FN Thomson Reuters Web of Science™ VR 1.0 PT J AU WILLIAMS, AE KLEINMAN, S GILCHER, RO JACKSON, CM MURPHY, EL SCHREIBER, GB MCENTIRE, R ZUCK, T AF WILLIAMS, AE KLEINMAN, S GILCHER, RO JACKSON, CM MURPHY, EL SCHREIBER, GB MCENTIRE, R ZUCK, T TI THE PREVALENCE OF INFECTIOUS-DISEASE MARKERS IN DIRECTED VS HOMOLOGOUS BLOOD DONATIONS SO TRANSFUSION LA English DT Meeting Abstract C1 NHLBI,RETROVIRUS EPIDEMIOL DONOR STUDY,BALTIMORE,MD. NHLBI,RETROVIRUS EPIDEMIOL DONOR STUDY,WASHINGTON,DC. NHLBI,RETROVIRUS EPIDEMIOL DONOR STUDY,LOS ANGELES,CA. NHLBI,RETROVIRUS EPIDEMIOL DONOR STUDY,OKLAHOMA CITY,OK. NHLBI,RETROVIRUS EPIDEMIOL DONOR STUDY,DETROIT,MI. NHLBI,RETROVIRUS EPIDEMIOL DONOR STUDY,SAN FRANCISCO,CA. NHLBI,RETROVIRUS EPIDEMIOL DONOR STUDY,ROCKVILLE,MD. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1992 VL 32 IS 8 SU S BP S45 EP S45 PG 1 WC Hematology SC Hematology GA JW378 UT WOS:A1992JW37800169 ER PT J AU MICHEJDA, M PETERS, SM BACHER, J HERNANDEZ, LF BELLANTI, JA AF MICHEJDA, M PETERS, SM BACHER, J HERNANDEZ, LF BELLANTI, JA TI INTRAUTERINE XENOTRANSPLANTATION OF BONE-MARROW STEM-CELLS IN NONHUMAN-PRIMATES SO TRANSPLANTATION LA English DT Note ID INUTERO TRANSPLANTATION; HLA-DQ; FETAL; POLYMORPHISM; DEFICIENCIES; EVOLUTION; ANEMIA; PROBE; DNA C1 NIH,NATL CTR RES RESOURCES,BETHESDA,MD 20832. NCI,FCRDC,ABL BASIC RES PROGRAM,FREDERICK,MD 21302. GEORGETOWN UNIV,MED CTR,INT CTR INTERDISCIPLINARY STUDIES IMMUNOL,DEPT MICROBIOL,WASHINGTON,DC 20007. RP MICHEJDA, M (reprint author), GEORGETOWN UNIV,MED CTR,INT CTR INTERDISCIPLINARY STUDIES IMMUNOL,DEPT PEDIAT,WASHINGTON,DC 20007, USA. OI Bellanti, Joseph/0000-0002-5038-7202 NR 37 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT PY 1992 VL 54 IS 4 BP 759 EP 762 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA JU603 UT WOS:A1992JU60300044 PM 1357795 ER PT J AU ARMSTRONG, DL WHITE, RE AF ARMSTRONG, DL WHITE, RE TI AN ENZYMATIC MECHANISM FOR POTASSIUM CHANNEL STIMULATION THROUGH PERTUSSIS-TOXIN-SENSITIVE G-PROTEINS SO TRENDS IN NEUROSCIENCES LA English DT Review ID GTP-BINDING-PROTEINS; ARACHIDONIC-ACID; K+-CHANNELS; CALCIUM-CHANNEL; 2ND MESSENGERS; SENSORY NEURONS; LIPOXYGENASE METABOLITES; APLYSIA-CALIFORNICA; NERVOUS-SYSTEM; MODULATION AB Many neurotransmitters inhibit secretion from electrically excitable cells by activating pertussis-toxin-sensitive G proteins that modulate voltage-gated ion channels. Recent electrophysiological studies of metabolically intact cells from mammalian and molluscan neuroendocrine systems have implicated protein phosphatases in this process. In this article David Armstrong and Richard White review these studies and suggest a biochemical pathway that might link one of the G proteins to protein phosphatase activity. RP NIEHS, CELLULAR & MOLEC PHARMACOL LAB, RES TRIANGLE PK, NC 27709 USA. NR 57 TC 60 Z9 61 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD OCT PY 1992 VL 15 IS 10 BP 403 EP 408 DI 10.1016/0166-2236(92)90192-B PG 6 WC Neurosciences SC Neurosciences & Neurology GA JQ369 UT WOS:A1992JQ36900016 PM 1279866 ER PT J AU STOJILKOVIC, SS CATT, KJ AF STOJILKOVIC, SS CATT, KJ TI NEUROENDOCRINE ACTIONS OF ENDOTHELINS SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID ANTERIOR-PITUITARY-CELLS; ADRENAL CHROMAFFIN CELLS; ZONA GLOMERULOSA CELLS; BINDING-SITES; VASOCONSTRICTOR PEPTIDE; INTRACELLULAR CALCIUM; RAT HYPOTHALAMUS; HUMAN-BRAIN; RECEPTOR; SECRETION AB Endothelins are produced in neuronal, pituitary and peripheral endocrine cells, and act through specific endothelin receptors (predominantly the ETA subtype) that are widely distributed in the neuroendocrine system. Endothelin receptors share a common signal transduction pathway with other Ca2+-mobilizing receptors, and endothelins induce IP3 and diacylglycerol production, and elevation of [Ca2+]i in many cell types, with kinetics similar to the cognate agonists. As reviewed here by Stanko Stojilkovic and Kevin Catt, the physiological consequences of endothelin-mediated cell signalling are relevant to the control of several neuroendocrine and endocrine activities including neuropeptide release, pituitary hormone secretion, gonadal and placental function, fluid and electrolyte homeostasis and glycogenolysis. RP STOJILKOVIC, SS (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892, USA. NR 50 TC 59 Z9 60 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD OCT PY 1992 VL 13 IS 10 BP 385 EP 391 DI 10.1016/0165-6147(92)90118-P PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JQ665 UT WOS:A1992JQ66500007 PM 1413087 ER PT J AU ALDROUBI, A TRUS, BL UNSER, M BOOY, FP STEVEN, AC AF ALDROUBI, A TRUS, BL UNSER, M BOOY, FP STEVEN, AC TI MAGNIFICATION MISMATCHES BETWEEN MICROGRAPHS - CORRECTIVE PROCEDURES AND IMPLICATIONS FOR STRUCTURAL-ANALYSIS SO ULTRAMICROSCOPY LA English DT Article; Proceedings Paper CT WORKSHOP ON QUANTITATIVE ELECTRON MICROSCOPY CY DEC, 1991 CL SCHLOSS RINGBERG, TEGERNSEE, GERMANY SP MAX PLANCK SOC HO SCHLOSS RINGBERG ID 3-DIMENSIONAL STRUCTURE; ELECTRON-MICROSCOPY; RECONSTRUCTION; VIRUS; MACROMOLECULES; CLASSIFICATION; CRYSTALLINE; PARTICLES; PROTEIN; IMAGES AB Quantitative structural analysis from electron micrographs of biological macromolecules inevitably requires the synthesis of data from many parts of the same micrograph and, ultimately, from multiple micrographs. Higher resolutions require the inclusion of progressively more data, and for the particles analyzed to be consistent to within ever more stringent limits. Disparities in magnification between micrographs or even within the field of one micrograph, arising from lens hysteresis or distortions, limit the resolution of such analyses. A quantitative assessment of this effect shows that its severity depends on the size of the particle under study: for particles that are 100 nm in diameter, for example, a 2% discrepancy in magnification restricts the resolution to approximately 5 nm. In this study, we derive and describe the properties of a family of algorithms designed for cross-calibrating the magnifications of particles from different micrographs, or from widely differing parts of the same micrograph. This approach is based on the assumption that all of the particles are of identical size: thus, it is applicable primarily to cryo-electron micrographs in which native dimensions are precisely preserved. As applied to icosahedral virus capsids, this procedure is accurate to within 0.1-0.2%, provided that at least five randomly oriented particles are included in the calculation. The algorithm is stable in the presence of noise levels typical of those encountered in practice, and is readily adaptable to non-isometric particles. It may also be used to discriminate subpopulations of subtly different sizes. C1 NIAMSD,DIV COMP RES & TECHNOL,COMP SYST LAB,BETHESDA,MD 20892. NIAMSD,STRUCT BIOL RES LAB,BETHESDA,MD 20892. RP ALDROUBI, A (reprint author), NIAMSD,BIOMED ENGN & INSTRUMENTAT PROGRAM,RM 3W13,BLDG 13,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008; Aldroubi, Akram/J-7186-2012 NR 25 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3991 J9 ULTRAMICROSCOPY JI Ultramicroscopy PD OCT PY 1992 VL 46 IS 1-4 BP 175 EP 188 DI 10.1016/0304-3991(92)90013-A PG 14 WC Microscopy SC Microscopy GA JZ064 UT WOS:A1992JZ06400012 PM 1336232 ER PT J AU KRAGEL, PJ TRAVIS, WD LUIBEL, FJ AF KRAGEL, PJ TRAVIS, WD LUIBEL, FJ TI SARCOMATOID RENAL-CARCINOMA WITH ANGIOSARCOMATOID COMPONENT - LIGHT MICROSCOPIC AND IMMUNOHISTOCHEMICAL STUDY SO UROLOGY LA English DT Article ID CELL CARCINOMA; PELVIS AB We describe a case of primary renal pelvic carcinoma which showed an unusual histologic pattern of anastomosing blood-filled channels lined by atypical cells. This angiosarcomatoid pattern merged with solid areas typical of renal carcinoma. Immunoperoxidase stains for cytokeratin and epithelial membrane antigen were positive in both the angiosarcomatoid and typical carcinomatous areas, while stains for factor VIII-related antigen and desmin were negative. Since primary renal angiosarcomas are rare neoplasms, the diagnosis of sarcomatoid renal carcinoma should be considered in primary renal neoplasms which show this angiosarcomatoid pattern. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. SHARP CABRILLO HOSP,DEPT PATHOL,SAN DIEGO,CA. NR 19 TC 9 Z9 10 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD OCT PY 1992 VL 40 IS 4 BP 381 EP 384 DI 10.1016/0090-4295(92)90396-E PG 4 WC Urology & Nephrology SC Urology & Nephrology GA KH662 UT WOS:A1992KH66200022 PM 1413363 ER PT J AU GOLDSTEIN, DJ TOYAMA, R DHAR, R SCHLEGEL, R AF GOLDSTEIN, DJ TOYAMA, R DHAR, R SCHLEGEL, R TI THE BPV-1 E5 ONCOPROTEIN EXPRESSED IN SCHIZOSACCHAROMYCES-POMBE EXHIBITS NORMAL BIOCHEMICAL-PROPERTIES AND BINDS TO THE ENDOGENOUS 16-KDA COMPONENT OF THE VACUOLAR PROTON-ATPASE SO VIROLOGY LA English DT Note ID PAPILLOMAVIRUS-E5 TRANSFORMING PROTEIN; OPEN READING FRAME; BOVINE PAPILLOMAVIRUS; VIRUS; GENE; ENCODES; TYPE-1 C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. RP GOLDSTEIN, DJ (reprint author), GEORGETOWN UNIV,SCH MED,DEPT PATHOL,3900 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. FU NCI NIH HHS [R01CA53371-01] NR 21 TC 16 Z9 16 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD OCT PY 1992 VL 190 IS 2 BP 889 EP 893 DI 10.1016/0042-6822(92)90932-F PG 5 WC Virology SC Virology GA JM765 UT WOS:A1992JM76500039 PM 1387753 ER PT J AU BERLIN, E BHATHENA, SJ JUDD, JT NAIR, PP PETERS, RC BHAGAVAN, HN BALLARDBARBASH, R TAYLOR, PR AF BERLIN, E BHATHENA, SJ JUDD, JT NAIR, PP PETERS, RC BHAGAVAN, HN BALLARDBARBASH, R TAYLOR, PR TI OMEGA-3-FATTY-ACID SUPPLEMENTATION STIMULATES ALPHA-TOCOPHEROL INCORPORATION IN ERYTHROCYTE-MEMBRANES IN ADULT MEN SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID VITAMIN-E; LIVER; PHOSPHOLIPIDS; HEART; OIL C1 USDA ARS, BELTSVILLE AGR RES CTR, CARBOHYDRATE NUTR LAB, BELTSVILLE, MD 20705 USA. HOFFMANN LA ROCHE INC, DEPT CLIN NUTR, NUTLEY, NJ 07110 USA. US DEPT HHS, NCI, DIV CANC PREVENT & CONTROL, CANC PREVENT STUDIES BRANCH, BETHESDA, MD 20014 USA. RP BERLIN, E (reprint author), USDA ARS, BELTSVILLE AGR RES CTR,LIPID NUTR LAB,BLDG 308, RM 109,BARC E, 10300 BALTIMORE AVE, BELTSVILLE, MD 20705 USA. NR 15 TC 3 Z9 3 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD SEP 30 PY 1992 VL 669 BP 322 EP 324 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA435 UT WOS:A1992KA43500031 ER PT J AU WANG, YH DHARIWAL, KR LEVINE, M AF WANG, YH DHARIWAL, KR LEVINE, M TI ASCORBIC-ACID BIOAVAILABILITY IN HUMANS - ASCORBIC-ACID IN PLASMA, SERUM, AND URINE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID INSITU KINETICS; CHROMAFFIN GRANULES RP WANG, YH (reprint author), NIDDKD, CELL BIOL & GENET LAB, BLDG 8, ROOM 415, BETHESDA, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD SEP 30 PY 1992 VL 669 BP 383 EP 386 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA435 UT WOS:A1992KA43500047 ER PT J AU BENINATI, S MUKHERJEE, AB AF BENINATI, S MUKHERJEE, AB TI A NOVEL TRANSGLUTAMINASE-CATALYZED POSTTRANSLATIONAL MODIFICATION OF HIV-1 ASPARTYL PROTEASE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RETROVIRAL PROTEASES; EPSILON-(GAMMA-GLUTAMYL)LYSINE; LIVER C1 NICHHD,BETHESDA,MD 20892. UNIV ROME TOR VERGATA,DEPT BIOL,I-00173 ROME,ITALY. OI Beninati, Simone/0000-0002-2704-0745 NR 16 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 30 PY 1992 VL 187 IS 3 BP 1211 EP 1218 DI 10.1016/0006-291X(92)90432-K PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JQ812 UT WOS:A1992JQ81200002 PM 1358064 ER PT J AU SAKAI, H PARK, SS KIKKAWA, Y AF SAKAI, H PARK, SS KIKKAWA, Y TI DIFFERENTIAL OXIDASE ACTIVITY OF HEPATIC AND PULMONARY MICROSOMAL CYTOCHROME-P-450 ISOZYMES AFTER TREATMENT WITH CYTOCHROME-P-450 INDUCERS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RAT-LIVER; INTERFERON INDUCERS; OXYGEN-TOXICITY; CYTOCHROMES-P-450; GENERATION; SYSTEM; INDUCIBILITY; PURIFICATION; PROTECTION; DAMAGE C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP SAKAI, H (reprint author), UNIV CALIF IRVINE,COLL MED,DEPT PATHOL,IRVINE,CA 92717, USA. FU NHLBI NIH HHS [HL-34688] NR 22 TC 12 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 30 PY 1992 VL 187 IS 3 BP 1262 EP 1269 DI 10.1016/0006-291X(92)90439-R PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JQ812 UT WOS:A1992JQ81200009 PM 1329733 ER PT J AU GROVER, S BOYE, O GETAHUN, Z BROSSI, A HAMEL, E AF GROVER, S BOYE, O GETAHUN, Z BROSSI, A HAMEL, E TI CHLOROACETATES OF 2-DEMETHYLTHIOCOLCHICINE AND 3-DEMETHYLTHIOCOLCHICINE - SPECIFIC COVALENT INTERACTIONS WITH TUBULIN WITH PREFERENTIAL LABELING OF THE BETA-SUBUNIT SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID COLCHICINE; THIOCOLCHICINE; SEPARATION; BINDING; ANALOGS C1 NIDDKD,STRUCT BIOL LAB,BETHESDA,MD 20892. RP GROVER, S (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892, USA. NR 17 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 30 PY 1992 VL 187 IS 3 BP 1350 EP 1358 DI 10.1016/0006-291X(92)90451-P PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JQ812 UT WOS:A1992JQ81200021 PM 1417811 ER PT J AU GRUSZECKAKOWALIK, E HAUGWITZ, RD ZALKOW, LH AF GRUSZECKAKOWALIK, E HAUGWITZ, RD ZALKOW, LH TI QUINOBENE, A NEW POTENT ANTI-HIV AGENT SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; LYMPHADENOPATHY-ASSOCIATED VIRUS; GIANT-CELL FORMATION; AURINTRICARBOXYLIC ACID; REVERSE-TRANSCRIPTASE; REPLICATION INVITRO; ANTIVIRAL ACTIVITY; RATIONAL DESIGN; INHIBITION; DERIVATIVES C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP GRUSZECKAKOWALIK, E (reprint author), GEORGIA INST TECHNOL,SCH CHEM & BIOCHEM,ATLANTA,GA 30332, USA. FU NCI NIH HHS [N01-CM-17550] NR 49 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 30 PY 1992 VL 187 IS 3 BP 1409 EP 1417 DI 10.1016/0006-291X(92)90459-X PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JQ812 UT WOS:A1992JQ81200029 PM 1417817 ER PT J AU GROHMANN, U PUCCETTI, P ROMANI, L BINAGLIA, L BIANCHI, R BELLADONNA, ML ULLRICH, SJ APPELLA, E FIORETTI, MC AF GROHMANN, U PUCCETTI, P ROMANI, L BINAGLIA, L BIANCHI, R BELLADONNA, ML ULLRICH, SJ APPELLA, E FIORETTI, MC TI IMMUNOGENIC TUMOR VARIANTS INDUCED BY DRUG-TREATMENT OF THE L5178Y LYMPHOMA - SEARCH FOR SEROLOGICALLY DEFINED ANTIGENS AT THE CLONAL LEVEL SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CELL-MEDIATED-IMMUNITY; CHEMICALLY XENOGENIZED TUMORS; POINT MUTATION; GENE; IDENTIFICATION; INVIVO AB Highly immunogenic tumor variants are generated by in vitro or in vivo treatment of the murine L5178Y lymphoma line with triazene derivatives. Most of these variants express new transplantation- and antibody-defined antigens that previous studies have shown to be closely related. One such 80-kDa protein on the surface of clone-D cells was found to be related to xenotropic MuLV gp70 molecules. To investigate the possible relevance of clone-D data to general properties of immunogenic variants in this tumor model system, polyclonal syngeneic antisera raised to a panel of immunogenic clones (including clone D) of the drug-treated L5178Y lymphoma line were employed in the immunoprecipitation of cell-surface and intrinsically labeled variant cells. In all clones, 1- and 2-dimensional electrophoretic analysis of the immunoprecipitates detected an antigen of approximately 80 kDa, and S-35-labeled 80-kDa molecules could be cross-precipitated from all clones by the panel of clone-specific antisera. In addition, 45- and 30-kDa components were also found in metabolically labeled variant cells. While the surface 80-kDa component was reactive with anti-xenotropic gp70 antibodies, the 30-kDa molecule was removed by anti-gag p30 antibody in sequential immunoprecipitation experiments. These data suggest that expression of aberrant, retrovirus-related proteins is a common finding in immunogenic cells of the drug-treated L5178Y lymphoma line. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP GROHMANN, U (reprint author), UNIV PERUGIA,DEPT EXPTL MED & BIOCHEM SCI,PHARMACOL SECT,I-06100 PERUGIA,ITALY. OI Puccetti, Paolo/0000-0001-6674-2128; Belladonna, Maria Laura/0000-0001-6522-0870; Grohmann, Ursula/0000-0001-7952-1850; Bianchi, Roberta/0000-0001-5914-4701 NR 21 TC 9 Z9 9 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 30 PY 1992 VL 52 IS 3 BP 372 EP 377 DI 10.1002/ijc.2910520308 PG 6 WC Oncology SC Oncology GA JQ496 UT WOS:A1992JQ49600007 PM 1399112 ER PT J AU ROSENBERG, PS GAIL, MH CARROLL, RJ AF ROSENBERG, PS GAIL, MH CARROLL, RJ TI ESTIMATING HIV PREVALENCE AND PROJECTING AIDS INCIDENCE IN THE UNITED-STATES - A MODEL THAT ACCOUNTS FOR THERAPY AND CHANGES IN THE SURVEILLANCE DEFINITION OF AIDS SO STATISTICS IN MEDICINE LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PLACEBO-CONTROLLED TRIAL; INTRAVENOUS DRUG-USERS; SHORT-TERM PROJECTIONS; VIRUS INFECTION; SAN-FRANCISCO; INCUBATION PERIOD; HOMOSEXUAL MEN; DOUBLE-BLIND; EPIDEMIC AB The AIDS incubation distribution is changing in calendar time because of treatment and changes in the surveillance definition of AIDS. To obtain reliable estimates of HIV prevalence and projections of AIDS incidence in the 1990s using the method of backcalculation, we constructed an appropriate incubation distribution for each calendar date of infection. We parameterized the impact of treatment on the incubation distribution by specifying the relative hazard for AIDS in treated versus untreated people as a function of duration of HIV infection. To account for trends in the incubation distribution, we modelled the prevalence of treatment, the distribution of treatment onset times, and the impact of the revision of the AIDS surveillance definition in 1987. We selected and evaluated backcalculation models based on consistency with external information. We defined a 'plausible range' of estimates that took into account uncertainty about the natural incubation distribution and treatment efficacy, as well as bootstrap assessment of stochastic error. Using these methods, we projected that national United States AIDS incidence will plateau during 1991-1994 at over 50,000 cases per year. Projections exhibited substantial systematic uncertainty, and we calculated a plausible range for AIDS incidence in 1994 of 42,300 to 70,700 cases. An estimated 628,000 to 988,000 cumulative HIV infections occurred as of 1 January 1991. After accounting for AIDS mortality, we estimated that 484,000 to 844,000 people were living with HIV infection on 1 January 1991. Favourable trends in HIV incidence appeared in gay men and intravenous drug users. Plausible ranges for our estimates overlapped with those from a 'stage model' approach to incorporating treatment effects in backcalculations. Our approach, however, tended to yield smaller estimates of epidemic size, mainly because the parameters used with the stage model implied that more treatment was in use and that treatment was more effective than in our model. C1 TEXAS A&M UNIV SYST,DEPT STAT,COLL STN,TX 77843. RP ROSENBERG, PS (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPIDEMIOL METHODS SECT,6130 EXECUT BLVD,EXECUT PLAZA N,ROOM 403,ROCKVILLE,MD 20892, USA. NR 39 TC 51 Z9 51 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 1992 VL 11 IS 13 BP 1633 EP 1655 DI 10.1002/sim.4780111302 PG 23 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA JZ965 UT WOS:A1992JZ96500001 PM 1485051 ER PT J AU NAM, JM FEARS, TR AF NAM, JM FEARS, TR TI CONTROL SAMPLE-SIZE WHEN CASES ARE GIVEN IN CONSTANT RATIO STRATUM-MATCHED CASE-CONTROL STUDIES SO STATISTICS IN MEDICINE LA English DT Article ID POWER; EFFICIENCY AB Strata-matched case-control studies based on a given number of cases and k times as many controls are common. We obtain a necessary and sufficient condition for there to exist a numerical solution for k with a desired level of a power. We derive the maximum power of the Cochran test, which may be less than one, when the number of cases is fixed. We provide an approximate formula for the minimum number of cases required for a specified power. There exists a numerical solution (that is, convergence of an iterative method) for k if the number of cases given is greater than this minimum number and no such a solution otherwise. We also show that the incremental gain in relative efficiency of the test with respect to k is diminished as k gets large. RP NAM, JM (reprint author), NCI,BIOSTAT BRANCH,6130 EXECUT BLVD,EPN 403,ROCKVILLE,MD 20892, USA. NR 17 TC 3 Z9 3 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 1992 VL 11 IS 13 BP 1759 EP 1766 DI 10.1002/sim.4780111309 PG 8 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA JZ965 UT WOS:A1992JZ96500008 PM 1485058 ER PT J AU POWERS, R CLORE, GM STAHL, SJ WINGFIELD, PT GRONENBORN, A AF POWERS, R CLORE, GM STAHL, SJ WINGFIELD, PT GRONENBORN, A TI ANALYSIS OF THE BACKBONE DYNAMICS OF THE RIBONUCLEASE-H DOMAIN OF THE HUMAN-IMMUNODEFICIENCY-VIRUS REVERSE-TRANSCRIPTASE USING N-15-RELAXATION MEASUREMENTS SO BIOCHEMISTRY LA English DT Article ID MODEL-FREE APPROACH; ESCHERICHIA-COLI; NMR-SPECTROSCOPY; MUTATIONAL ANALYSIS; SECONDARY STRUCTURE; HIV-1; PROTEINS; MACROMOLECULES; ENDONUCLEASE; RELAXATION AB The backbone dynamics of the uniformly N-15-labeled ribonuclease H (RNase H) domain of human immunodeficiency virus (HIV-1) reverse transcriptase have been investigated using two-dimensional inverse-detected heteronuclear N-15-H-1 NMR spectroscopy. N-15 T1,T2, and nuclear Overhauser enhancement (NOE) data were obtained for 107 out of a total of 134 backbone amide groups. The overall rotational correlation time (tau(R)) for the protein at 26-degrees-C is 10.4 ns. The backbone N-H vectors for all the measurable residues exhibit very fast motions on a time scale of less-than-or-equal-to 20 ps. The 15N relaxation data for only 14 residues can be explained by this single internal motion alone. A further 39 residues display a second motion on a time scale ranging from 28.8 ps to 3.9 ns, while another 15 residues are characterized by an additional motion on the 170-ns to 2.25-ms time scale resulting in N-15 T2 exchange line broadening. There are 39 residues that exhibit both the additional N-15 T2 exchange line broadening and the slow (28.8 ps-3.9 ns) internal motion. Thus, the RNase H domain experiences extensive mobility throughout its structure as evidenced by the 93 residues which exhibit multiple modes of motion. Distinctly mobile regions of the protein are identified by large decreases in the overall order parameter (S2) and correspond to the C-terminal residues and the loop regions between beta-strands beta1 and beta2 and between alpha-helix alpha(B) and beta-strand beta4. The high mobility of the C-terminus is of particular interest since one stretch of the sequence in this region of the protein constitutes part of the proposed substrate binding site. Thus, a highly flexible or partially folded binding pocket could explain the lack of enzymatic activity observed for this particular HIV-1 RNase H domain. C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. NIH,PROT EXPRESS LAB,OFF DIRECTOR,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 39 TC 76 Z9 76 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 29 PY 1992 VL 31 IS 38 BP 9150 EP 9157 DI 10.1021/bi00153a006 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JQ372 UT WOS:A1992JQ37200006 PM 1382587 ER PT J AU BOUMPAS, DT AUSTIN, HA VAUGHN, EM KLIPPEL, JH STEINBERG, AD YARBORO, CH BALOW, JE AF BOUMPAS, DT AUSTIN, HA VAUGHN, EM KLIPPEL, JH STEINBERG, AD YARBORO, CH BALOW, JE TI CONTROLLED TRIAL OF PULSE METHYLPREDNISOLONE VERSUS 2 REGIMENS OF PULSE CYCLOPHOSPHAMIDE IN SEVERE LUPUS NEPHRITIS SO LANCET LA English DT Article ID INTRAVENOUS CYCLOPHOSPHAMIDE; THERAPY; ERYTHEMATOSUS; PREDNISONE; DRUGS AB Pulse cyclophosphamide is more effective than prednisone alone in preventing renal failure in lupus nephritis. We undertook a randomised, controlled trial to find out whether pulse methylprednisolone could equal pulse cyclophosphamide in preserving renal function in patients with lupus nephritis, and whether there was a difference between long and short courses of pulse cyclophosphamide in preventing exacerbations. 65 patients (60 female, 5 male; median [range] age 29 [10-48] years) with severe lupus nephritis were assigned randomly to monthly pulse methylprednisolone for 6 months (25 patients), monthly pulse cyclophosphamide for 6 months (20), or monthly cyclophosphamide for 6 months followed by quarterly pulse cyclophosphamide for 2 additional years (20). Patients treated with pulse methylprednisolone had a higher probability of doubling serum creatinine than those treated with long-course cyclophosphamide (p<0.04). Risk of doubling creatinine was not significantly different between short and long course cyclophosphamide. However, patients treated with short-course cyclophosphamide had a higher probability of exacerbations than those treated with long-course cyclophosphamide (p<0.01). An extended course of pulse cyclophosphamide is more effective than 6 months of pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis. Addition of a quarterly maintenance regimen to monthly pulse cyclophosphamide reduces the rate of exacerbations. C1 NIAMSD,CTR CLIN,DEPT NURSING,BETHESDA,MD. NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD. RP BOUMPAS, DT (reprint author), NIDDK,KIDNEY DIS SECT,BLDG 10,ROOM 3N-112,BETHESDA,MD 20892, USA. NR 27 TC 555 Z9 585 U1 0 U2 6 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD SEP 26 PY 1992 VL 340 IS 8822 BP 741 EP 745 DI 10.1016/0140-6736(92)92292-N PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JP869 UT WOS:A1992JP86900001 PM 1356175 ER PT J AU ROSE, K SIMONA, MG SAVOY, LA REGAMEY, PO GREEN, BN CLORE, GM GRONENBORN, AM WINGFIELD, PT AF ROSE, K SIMONA, MG SAVOY, LA REGAMEY, PO GREEN, BN CLORE, GM GRONENBORN, AM WINGFIELD, PT TI PYRUVIC-ACID IS ATTACHED THROUGH ITS CENTRAL CARBON-ATOM TO THE AMINO TERMINUS OF THE RECOMBINANT DNA-DERIVED DNA-BINDING PROTEIN NER OF BACTERIOPHAGE-MU SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELECTROSPRAY AB Ner protein of bacteriophage Mu, produced by recombinant DNA techniques in Escherichia coli, has been found to possess a molecule of pyruvic acid attached covalently through carbon-2 to the amino-terminal cysteine residue. The intact protein and the amino-terminal chymotryptic peptide were found by mass spectrometry to be 70 mass units heavier than expected. The modified peptide was unstable under mildly acid or mildly basic conditions. Two-dimensional nuclear magnetic resonance spectroscopy of the modified and unmodified forms of the amino-terminal chymotryptic peptide was consistent with the presence of pyruvate linked through carbon-2 to the amino-terminal Cys residue. Treatment of the modified form with 2,4-dinitrophenylhydrazine in acid medium led to the expected hydrazone of pyruvic acid, which was identified by high pressure liquid chromatography. Of the two proteins known to be modified by pyruvate through its central carbon (the other being human adult hemoglobin, in which the modified form represents only a very minor fraction), Ner is the first protein found to be modified quantitatively. Given the instability of the modification, it may be more prevalent than recognized hitherto. Incubation with 2,4-dinitrophenylhydrazine may offer a useful means of detecting the presence of pyruvate linked to proteins in this way. C1 VG BIOTECH,ALTRINCHAM WA14 5RZ,CHESHIRE,ENGLAND. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. PFIZER INC,CENT RES,GROTON,CT 06340. RP ROSE, K (reprint author), CTR MED UNIV GENEVA,DEPT BIOCHIM MED,1 RUE MICHEL SERVET,CH-1211 GENEVA 4,SWITZERLAND. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 7 TC 5 Z9 7 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1992 VL 267 IS 27 BP 19101 EP 19106 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JP593 UT WOS:A1992JP59300017 PM 1388164 ER PT J AU MONTROSERAFIZADEH, C BLACKMON, DL HAMOSH, A OLIVA, MM HAWKINS, AL CURRISTIN, SM GRIFFIN, CA YANG, VW GUGGINO, WB CUTTING, GR MONTROSE, MH AF MONTROSERAFIZADEH, C BLACKMON, DL HAMOSH, A OLIVA, MM HAWKINS, AL CURRISTIN, SM GRIFFIN, CA YANG, VW GUGGINO, WB CUTTING, GR MONTROSE, MH TI REGULATION OF CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) GENE-TRANSCRIPTION AND ALTERNATIVE RNA SPLICING IN A MODEL OF DEVELOPING INTESTINAL EPITHELIUM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA; NUCLEOTIDE-BINDING; CHLORIDE CHANNEL; RIBONUCLEIC-ACID; CELL POLARITY; EXPRESSION; DIFFERENTIATION; IDENTIFICATION; GENERATION; TRANSPORT AB Transcriptional and post-transcriptional regulation of CFTR (cystic fibrosis transmembrane conductance regulator) gene expression was studied in HT29 cells. It is known that the abundance of CFTR mRNA increases during differentiation of pluripotent HT29-18 cells and is maintained at high levels in the stably differentiated HT29-18-C1 subclone. Nuclear run-on assays suggest that increased transcription of the CFTR gene explains the increased abundance of total CFTR mRNA in differentiated HT29 cells. The increased transcription cannot be ascribed to cell cycle-dependent expression of the CFTR gene or to changes in CFTR gene copy number between subcloned cells. Similar to native tissue cells, differentiated HT29 cells contain low copy numbers of CFTR transcripts (1-5/cell), and a portion of the CFTR transcripts are alternatively spliced to remove exon 9 (and make 9- mRNA). During differentiation of HT29-18 cells, the absolute amount of full-length CFTR mRNA increases 8-fold, whereas the amount of 9- mRNA increases 18-fold. The fraction of 9- mRNA in the CFTR mRNA pool is increased in differentiated HT29 cells. The results show that gene transcription regulates the abundance of CFTR transcripts and that regulatory control of alternative RNA splicing may also be a cellular mechanism to modulate CFTR function. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,ROSS RES BLDG,RM 930,720 RUTLAND ST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. FU NHLBI NIH HHS [HL47122]; NIGMS NIH HHS [GM41015] NR 47 TC 10 Z9 10 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1992 VL 267 IS 27 BP 19299 EP 19305 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JP593 UT WOS:A1992JP59300044 PM 1382071 ER PT J AU GUO, NH KRUTZSCH, HC NEGRE, E ZABRENETZKY, VS ROBERTS, DD AF GUO, NH KRUTZSCH, HC NEGRE, E ZABRENETZKY, VS ROBERTS, DD TI HEPARIN-BINDING PEPTIDES FROM THE TYPE-I REPEATS OF THROMBOSPONDIN - STRUCTURAL REQUIREMENTS FOR HEPARIN BINDING AND PROMOTION OF MELANOMA CELL-ADHESION AND CHEMOTAXIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLATELET THROMBOSPONDIN; SULFATED GLYCOLIPIDS; ENDOTHELIAL-CELLS; GLYCOSAMINOGLYCAN SYNTHESIS; ALTERED METABOLISM; DIFFERENT PROTEINS; NEURITE OUTGROWTH; LIGAND-BINDING; RECEPTOR; ATTACHMENT AB Synthetic peptides derived from the type I repeats of human platelet thrombospondin containing a consensus sequence Trp-Ser-Xaa-Trp bind to heparin, promote cell adhesion, and inhibit heparin-dependent interactions of melanoma cells with extracellular matrix components (Guo, N. H., Krutzsch, H. C., Negre, E., Vogel, T., Blake, D. A., and Roberts, D. D. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 3040-3044). In the present study, we further examined the structural requirements for activity of these peptides. The minimal active sequence for heparin or sulfatide binding based on inhibition studies is Trp-Ser-Pro-Trp, although an octapeptide is required for optimal activity. The 2 Trp residues and the Ser residue are essential. Peptides with more than 2 residues between the Trp residues are inactive. The Pro residue is essential for activity of the pentapeptide Trp-Ser-Pro-Trp-Ser, but some larger peptides with substitutions for the Pro residue are active. For direct high affinity binding to heparin, both the consensus sequence and a flanking sequence of basic amino acids are essential. Peptides containing the consensus sequence promote cell adhesion and act cooperatively with the adjacent basic amino acid sequence to promote cell spreading. Chemical modification of the Trp residues in the peptides with amino-terminal basic amino acids abolished both cell adhesion and heparin-binding. Peptides containing the consensus sequence and basic amino acids are chemotactic for A2058 human melanoma cells. The functional importance of this novel heparin and sulfatide-binding motif is suggested by its conservation in other members of the thrombospondin gene family, complement components, and in many members of the cytokine receptor and transforming growth factor beta superfamilies. C1 NCI,PATHOL LAB,BLDG 10,ROOM 2A33,BETHESDA,MD 20892. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 48 TC 105 Z9 105 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1992 VL 267 IS 27 BP 19349 EP 19355 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JP593 UT WOS:A1992JP59300051 PM 1527055 ER PT J AU MAHONEY, CW SHUMAN, J MCKNIGHT, SL CHEN, HC HUANG, KP AF MAHONEY, CW SHUMAN, J MCKNIGHT, SL CHEN, HC HUANG, KP TI PHOSPHORYLATION OF CCAAT-ENHANCER BINDING-PROTEIN BY PROTEIN-KINASE-C ATTENUATES SITE-SELECTIVE DNA-BINDING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR FACTOR CREB; LEUCINE ZIPPER; TRANSCRIPTION FACTOR; NUCLEOTIDE-SEQUENCE; NEUROSPORA-CRASSA; CYCLIC-AMP; 3T3 CELLS; GENE; EXPRESSION; ONCOGENE AB Four DNA-recombinant proteins, corresponding to the DNA-binding domain of CCAAT/enhancer binding protein (C/EBP), were phosphorylated in vitro by protein kinase C (PKC). High-performance liquid chromatography-peptide mapping of P-32-labeled C/EBP indicated the presence of three major P-32-labeled peptides: S299 (P)RDK, AKKS277 (P)VDK, and GAAGLP-GPGGS248 (P)LK. Phosphorylation of C/EBP by PKC or M-kinase resulted in an attenuation of binding to a P-32-labeled CCAAT oligodeoxynucleotide. Three other truncated forms of C/EBP, C/EBP87, C/EBP87S-C, and C/EBP60, were studied to define the sites of phosphorylation affecting DNA binding. Phosphorylation of the C/EBP87, containing sites Ser299 and Ser277, and C/EBP60, containing only site Ser299, by PKC also resulted in attenuation of DNA binding. In contrast, phosphorylation of C/EBP87S-C, which retained Ser277 but had a Cys in place of Ser299, had no effect on DNA binding. Ser299 could not be phosphorylated by PKC if the protein is already bound to specific DNA. Phosphorylation of intact C/EBP from liver nuclear extract by PKC or M-kinase occurred at Ser299 and Ser277 and at an additional site, as demonstrated by immunoprecipitation and peptide mapping. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 10,RM B1L400,BETHESDA,MD 20892. CARNEGIE INST WASHINGTON,DEPT EMBRYOL,BALTIMORE,MD 21210. NR 52 TC 109 Z9 110 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1992 VL 267 IS 27 BP 19396 EP 19403 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JP593 UT WOS:A1992JP59300059 PM 1527059 ER PT J AU KIM, IY VERES, Z STADTMAN, TC AF KIM, IY VERES, Z STADTMAN, TC TI ESCHERICHIA-COLI MUTANT SELD ENZYMES - THE CYSTEINE-17 RESIDUE IS ESSENTIAL FOR SELENOPHOSPHATE FORMATION FROM ATP AND SELENIDE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BACTERIOPHAGE-T7 RNA-POLYMERASE; SELENOCYSTEINE SYNTHASE; GENES; NUCLEOSIDE; EXPRESSION; SEQUENCE; CHAIN AB Synthesis of a labile selenium donor compound, selenophosphate, from selenide and ATP by the Escherichia coli SELD enzyme was reported previously from this laboratory. From the gene sequence, SELD is a 37-kDa protein that contains 7 cysteine residues, 2 of which are located at positions 17 and 19 in the sequence -Gly-Ala-Cys-Gly-Cys-Lys-Ile-(Leinfelder, W., Forchhammer, K., Veprek, B., Zehelein, E., and Bock, A. (1990) Proc. Natl. Acad. Sci. U. S. A. 73, 543-547). Inactivation of the enzyme by alkylation with iodoacetamide indicated that at least 1 cysteine residue in the protein is essential for enzyme activity. To test the possibility that the Cys17 and/or Cys19 residue might be essential, these were changed to serine residues by site-specific mutagenesis. The biological activities of the wild type and mutant proteins were studied using E. coli MB08 (selD-) transformed with plasmids containing the selD genes. The plasmid containing the Cys17-mutated gene failed to complement MB08, whereas the Cys19-mutated gene was indistinguishable from wild type. The mutant proteins, like the wild type enzyme, bound to an ATP-agarose matrix, showing that their affinities for ATP were unimpaired. Selenide-dependent formation of AMP from ATP was abolished by mutation of Cys17, but the Cys19 mutation had no effect on the ability of the enzyme to catalyze the reaction. These results indicate that Cys17 has an essential role in the catalytic process that leads to the formation of selenophosphate from ATP and selenide. C1 NHLBI, BIOCHEM LAB, BLDG 3, RM 108, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. HUNGARIAN ACAD SCI, CENT RES INST CHEM, H-1525 BUDAPEST, HUNGARY. NR 23 TC 45 Z9 47 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1992 VL 267 IS 27 BP 19650 EP 19654 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JP593 UT WOS:A1992JP59300094 PM 1527085 ER PT J AU COLLUM, RG FISHER, PE DATTA, M MELLIS, S THIELE, C HUEBNER, K CROCE, CM ISRAEL, MA THEIL, T MOROY, T DEPINHO, R ALT, FW AF COLLUM, RG FISHER, PE DATTA, M MELLIS, S THIELE, C HUEBNER, K CROCE, CM ISRAEL, MA THEIL, T MOROY, T DEPINHO, R ALT, FW TI A NOVEL POU HOMEODOMAIN GENE SPECIFICALLY EXPRESSED IN CELLS OF THE DEVELOPING MAMMALIAN NERVOUS-SYSTEM SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOMAIN PROTEIN; EWINGS-SARCOMA; DNA-BINDING; SEQUENCE; TRANSCRIPTION; FAMILY; NEUROEPITHELIOMA; TRANSLOCATION; CONTAINS; TUMORS AB We report the isolation of a novel human POU domain encoding gene named RDC-1. The POU domain of the RDC-1 encoded protein is highly related to the POU domain potentially encoded by the rat brain-3 sequence and to that of the Drosophila I-POU protein; outside of the POU region, RDC-1 is unrelated to any previously characterized protein. The RDC-1 gene is expressed almost exclusively in normal tissues and transformed cells of neural origin. In the developing mouse and human fetus, RDC-1 is expressed in a spatially and temporally restricted pattern that suggests a critical role in the differentiation of neuronal tissues. In addition, RDC-1 is expressed in a unique subset of tumors of the peripheral nervous system including neuroepitheliomas and Ewing's sarcomas but not neuroblastomas. Based on its unique structural characteristics and expression pattern, we discuss potential functions for the RDC-1 protein. C1 COLUMBIA UNIV COLL PHYS & SURG,HOWARD HUGHES MED INST,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT BIOCHEM,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT MICROBIOL,NEW YORK,NY 10032. ALBERT EINSTEIN UNIV,DEPT MICROBIOL,BRONX,NY. NIH,MOLEC GENET SECT,PEDIAT BRANCH,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON CANC CTR,PHILADELPHIA,PA 19107. UNIV CALIF SAN FRANCISCO,DEPT NEUROL SURG & PEDIAT,BRAIN TUMOR RES CTR,SAN FRANCISCO,CA 94143. UNIV MARBURG,INST MOLEK BIOL & TUMORFORSCH,W-3550 MARBURG,GERMANY. RI Moroy, Tarik/D-9923-2011 NR 27 TC 48 Z9 49 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 25 PY 1992 VL 20 IS 18 BP 4919 EP 4925 DI 10.1093/nar/20.18.4919 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR354 UT WOS:A1992JR35400033 PM 1357630 ER PT J AU WHITEHURST, C HENNEY, HR MAX, EE SCHROEDER, HW STUBER, F SIMINOVITCH, KA GARRARD, WT AF WHITEHURST, C HENNEY, HR MAX, EE SCHROEDER, HW STUBER, F SIMINOVITCH, KA GARRARD, WT TI NUCLEOTIDE-SEQUENCE OF THE INTRON OF THE GERMLINE HUMAN CHI IMMUNOGLOBULIN GENE CONNECTING THE J-REGIONS AND C-REGIONS REVEALS A MATRIX ASSOCIATION REGION (MAR) NEXT TO THE ENHANCER SO NUCLEIC ACIDS RESEARCH LA English DT Note ID CHROMOSOMAL LOOP ANCHORAGE; STABLE INTEGRATION; TOPOISOMERASE-II; RECOMBINATION; EXPRESSION; ELEMENTS; SITES C1 UNIV HOUSTON, DEPT BIOL, HOUSTON, TX 77204 USA. NIH, BETHESDA, MD 20892 USA. UNIV ALABAMA, DEPT MED, BIRMINGHAM, AL 35294 USA. UNIV ALABAMA, DEPT MICROBIOL, BIRMINGHAM, AL 35294 USA. MT SINAI HOSP, DEPT MED, TORONTO M5G 1X5, ONTARIO, CANADA. RP WHITEHURST, C (reprint author), UNIV TEXAS, SW MED CTR, DEPT BIOCHEM, DALLAS, TX 75235 USA. RI Siminovitch, Katherine/K-1475-2013 FU NIGMS NIH HHS [GM22201, GM29935, GM31689] NR 14 TC 30 Z9 30 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 25 PY 1992 VL 20 IS 18 BP 4929 EP 4930 DI 10.1093/nar/20.18.4929 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR354 UT WOS:A1992JR35400036 PM 1408808 ER PT J AU FRANZOSO, G BOURS, V PARK, S TOMITAYAMAGUCHI, M KELLY, K SIEBENLIST, U AF FRANZOSO, G BOURS, V PARK, S TOMITAYAMAGUCHI, M KELLY, K SIEBENLIST, U TI THE CANDIDATE ONCOPROTEIN BCL-3 IS AN ANTAGONIST OF P50/NF-KAPPA-B-MEDIATED INHIBITION SO NATURE LA English DT Article ID NF-KAPPA-B; DNA-BINDING SUBUNIT; REL-ASSOCIATED PP40; CELL-CYCLE CONTROL; HUMAN T-CELLS; P65 SUBUNIT; TRANSCRIPTION; CLONING; HOMOLOGY; PROTEIN AB THE candidate oncogene bcl-3 was discovered as a translocation into the immunoglobulin alpha-locus in some cases of B-cell chronic lymphocytic leukaemias1. The protein Bcl-3 contains seven so-called ankyrin repeats. Similar repeat motifs are found in a number of diverse regulatory proteins but the motifs of Bcl-3 are most closely related to those found in I-kappa-B proteins in which the ankyrin repeat domain is thought to be directly involved in inhibition of NF-kappa-B activity. No biological function has yet been described for Bcl-3, but it was noted recently2 that Bcl-3 interferes with DNA-binding of the p50 subunit of NF-kappa-B in vitro. Here we demonstrate that Bcl-3 can aid kappa-B site-dependent transcription in vivo by counteracting the inhibitory effects of p50/NF-kappa-B homodimers. Bcl-3 may therefore aid activation of select NF-kappa-B-regulated genes, including those of the human immunodeficiency virus. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 35 TC 273 Z9 276 U1 1 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 24 PY 1992 VL 359 IS 6393 BP 339 EP 342 DI 10.1038/359339a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JP503 UT WOS:A1992JP50300063 PM 1406939 ER PT J AU ASCHERIO, A CHASE, R COTE, T DEHAES, G HOSKINS, E LAAOUEJ, J PASSEY, M QADERI, S SHUQAIDEF, S SMITH, MC ZAIDI, S AF ASCHERIO, A CHASE, R COTE, T DEHAES, G HOSKINS, E LAAOUEJ, J PASSEY, M QADERI, S SHUQAIDEF, S SMITH, MC ZAIDI, S TI EFFECT OF THE GULF-WAR ON INFANT AND CHILD-MORTALITY IN IRAQ SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article AB Background. Increased malnutrition and morbidity among Iraqi children after the onset of the Persian Gulf war have been reported by several fact-finding missions. The magnitude of the effect of the war and the economic embargo on child mortality remains uncertain, however. Methods. We conducted a survey of 271 clusters of 25 to 30 households each, chosen as a representative sample of the Iraqi population. The households were selected and the interviews conducted by an international team of public health professionals independent of Iraqi authorities. In each household all women 15 to 49 years of age were interviewed, and the dates of birth and death of all children born on or after January 1, 1985, were recorded. Results. The study population included 16,076 children, 768 of whom died during the period surveyed (January 1, 1985, to August 31, 1991). The age-adjusted relative mortality for the period after the war began, as compared with the period before the war, was 3.2 (95 percent confidence interval, 2.8 to 3.7). No material change in the relative risk was observed after adjustment for region of residence, maternal education, and maternal age. The increase in mortality after the onset of the war was higher among children 1 to less than 12 months old (relative risk, 4.1; 95 percent confidence interval, 3.3 to 5.2) and among those 12 to less than 60 months old (relative risk, 3.8; 95 percent confidence interval, 2.6 to 5.4) than among those less than 1 month old (relative risk, 1.8; 95 percent confidence interval, 1.4 to 2.4). The association between the war and mortality was stronger in northern Iraq (relative risk, 5.3) and southern Iraq (relative risk, 3.4) than in the central areas (relative risk, 1.9) or in Baghdad (relative risk, 1.7). Conclusions. These results provide strong evidence that the Gulf war and trade sanctions caused a threefold increase in mortality among Iraqi children under five years of age. We estimate that an excess of more than 46,900 children died between January and August 1991. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT POPULAT SCI & INT HLTH,BOSTON,MA 02115. MED AID THIRD WORLD,BRUSSELS,BELGIUM. JORDAN UNIV SCI & TECHNOL,IRBID,JORDAN. NIH,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. UNIV OXFORD,OXFORD,ENGLAND. MCMASTER UNIV,DEPT CLIN EPIDEMIOL & BIOSTAT,HAMILTON L8S 4L8,ONTARIO,CANADA. PAPUA NEW GUINEA INST MED RES,GOROKA,PAPUA N GUINEA. NR 19 TC 71 Z9 71 U1 0 U2 5 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 24 PY 1992 VL 327 IS 13 BP 931 EP 936 DI 10.1056/NEJM199209243271306 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA JP014 UT WOS:A1992JP01400006 PM 1513350 ER PT J AU RIZZO, P TINELLO, C PUNTURIERI, A TANIUCHI, H AF RIZZO, P TINELLO, C PUNTURIERI, A TANIUCHI, H TI A STUDY OF HYDROGEN-EXCHANGE OF MONOCLONAL-ANTIBODIES - SPECIFICITY OF THE ANTIGEN-BINDING INDUCED CONFORMATIONAL STABILIZATION SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE HYDROGEN EXCHANGE; MONOCLONAL ANTIBODY; FAB FRAGMENT; ANTIGEN INDUCED STABILIZATION; ANTIGEN RECOGNITION ID 3-DIMENSIONAL STRUCTURE; GUANIDINE-HYDROCHLORIDE; IMMUNOGLOBULIN-G; CYTOCHROME-C; COMPLEX; FRAGMENT; DOMAINS; SITE; FAB AB Amide-hydrogen exchange of three anti-yeast iso-1-cytochrome-c IgG monoclonal antibodies and the Fab, prepared from one of them, were studied by infrared spectrophotometry in the presence and absence of the deuterated immunogen and evolutionarily related species (the deuterated immunogen contained a population of a dimer. Each subunit of the dimer appeared to bind to the antibodies in a manner similar to the monomer), The number of hydrogens of the antibodies whose exchange was suppressed on binding to the immunogen was found to exceed that estimated for the residues shielded by the immunogen. Analysis of the data suggests that such suppression of hydrogen exchange occurs mainly for the Fab domains, but not for the Fc. One of the antibodies showed two distinct classes of amide-hydrogens. Class-1 hydrogens (approx. 36/site) exchange faster than class 2 (approx. 37/site). The exchange of class-1 hydrogens was suppressed by binding to the immunogen, but not to the evolutionarily related species. The exchange of class-2 hydrogens was suppressed by binding to the evolutionarily related species, as well as to the immunogen. Thus, the suppression of exchange of class-I hydrogens appears to occur by some kind of conformational stabilization, the mechanism of which differentiates between the deuterated immunogen and the evolutionarily related species. Evidence suggests that the trans-interactions of the Fab domains may modulate the hydrogen exchange. If it is assumed that the antigen-binding strengthens the trans-interactions in such a way that the exchange of the slower exchanging hydrogens is suppressed, this could explain the suppression of exchange of class-2 hydrogens. C1 NIDDKD,CHEM BIOL LAB,BETHESDA,MD 20892. NR 41 TC 11 Z9 12 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD SEP 23 PY 1992 VL 1159 IS 2 BP 169 EP 178 DI 10.1016/0167-4838(92)90022-6 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JT180 UT WOS:A1992JT18000009 PM 1327157 ER PT J AU ELMALLAKH, RS AF ELMALLAKH, RS TI INTENTIONAL SELF-INJECTION WITH HIV SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP ELMALLAKH, RS (reprint author), NIMH,HOSP NEUROPSYCHIAT RES,WASHINGTON,DC 20032, USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 23 PY 1992 VL 268 IS 12 BP 1541 EP 1541 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JN256 UT WOS:A1992JN25600020 PM 1518107 ER PT J AU BERGER, CJ MURABITO, JM EVANS, JC ANDERSON, KM LEVY, D AF BERGER, CJ MURABITO, JM EVANS, JC ANDERSON, KM LEVY, D TI PROGNOSIS AFTER 1ST MYOCARDIAL-INFARCTION - COMPARISON OF Q-WAVE AND NON-Q-WAVE MYOCARDIAL-INFARCTION IN THE FRAMINGHAM HEART-STUDY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LONG-TERM PROGNOSIS; CLINICAL-SIGNIFICANCE; NATURAL-HISTORY; QRS COMPLEX; ST SEGMENT; PREVALENCE; LOCATION; EXTENSION; MORTALITY; ANTERIOR AB Objective.-To compare the short- and long-term prognosis following a first Q-wave or non-Q-wave myocardial infarction. Design.-Cohort study with a mean follow-up period of 5.1+/-4.9 years. Setting.-Population-based. Participants.-Framingham (Mass) Heart Study subjects with an initial recognized myocardial infarction during a 17-year period were studied, including 227 men and 136 women with a mean age of 67.2 years. Seventy-seven percent of first infarctions were Q-wave infarctions and 23% were non-Q-wave infarctions. Main Outcome Measures.-Reinfarction and death from coronary heart disease. Results.-During the follow-up period, subjects with non-Q-wave infarctions had a significantly higher rate of reinfarction than subjects in the Q-wave group (P=.02 for the entire follow-up). The 10-year reinfarction rates were 44.8% vs 27.4%. When analyzed separately by age and sex, differences in reinfarction rates were only noted in men and in those under the age of 65 years. There were no differences in coronary heart disease death rates based on Q-wave status, even when examined separately by age and sex. Multivariate analysis revealed a 1.8-fold higher risk of reinfarction in the non-Q-wave group (95% confidence interval, 1.1 to 3.1), and also demonstrated that baseline hypertension was an independent risk factor for predicting reinfarction (relative risk, 1.8; 95% confidence interval, 1.1 to 3.2). There were no differences in the rates of sudden death or all-cause mortality following the two types of myocardial infarction. Additionally, subjects with a first Q-wave infarction had a higher rate of subsequent congestive heart failure, while those with non-Q-wave infarctions had a significantly higher rate of coronary insufficiency (unstable angina with transient ST-T wave abnormalities). Conclusions.-These results confirm and extend findings from prior studies that have identified patients with first non-Q-wave myocardial infarctions as potentially unstable, with greater subsequent morbidity and similar mortality to their counter-parts with Q-wave infarctions. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,5 THURBER ST,FRAMINGHAM,MA 01701. BETH ISRAEL HOSP,DIV CARDIOVASC,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02118. NR 45 TC 76 Z9 79 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 23 PY 1992 VL 268 IS 12 BP 1545 EP 1551 DI 10.1001/jama.268.12.1545 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA JN256 UT WOS:A1992JN25600024 PM 1518109 ER PT J AU HAMAGUCHI, N CHARIFSON, P DARDEN, T XIAO, L PADMANABHAN, K TULINSKY, A HISKEY, R PEDERSEN, L AF HAMAGUCHI, N CHARIFSON, P DARDEN, T XIAO, L PADMANABHAN, K TULINSKY, A HISKEY, R PEDERSEN, L TI MOLECULAR-DYNAMICS SIMULATION OF BOVINE PROTHROMBIN FRAGMENT-1 IN THE PRESENCE OF CALCIUM-IONS SO BIOCHEMISTRY LA English DT Article ID HUMAN PLASMINOGEN KRINGLE-4; GAMMA-CARBOXYGLUTAMIC ACID; NUCLEIC-ACIDS; FORCE-FIELD; RESOLUTION; PROTEINS; BINDING; DOMAIN; MODEL AB Early solvation-induced structural reorganization of calcium prothrombin fragment 1 is simulated with molecular dynamics. Initial coordinates are those of the 2.2-angstrom resolution crystal structure [Soriano-Garcia, M., Padmanabhan, K., de Vos, A. M., & Tulinsky, A. (1992) Biochemistry 31, 2554-2556]. The molecular dynamics code AMBER, appropriately modified to include long-range (less-than-or-equal-to 22.0 angstrom) ionic forces, was employed. The solution structure appears to equilibrate within 100 ps. Although minor changes are seen in various structural domains, the early solution structure basically maintains an intricate network of nine gamma-carboxyglutamic acid (Gla) residues encapsulating seven calcium ions. However, the Gla domain moves with respect to the kringle domain. This motion is mainly due to the movement of Ser34-Leu35 that appears to be a flexible hinge between the domains. The N-terminus of Ala1 is in a tightly bound complex with three Gla residues that remains stable in the solution structure when the long-range electrostatic cutoff is employed and the near planar alignment of the seven calcium ions is only slightly distorted. The simulation structure is discussed in terms of experiments that studied calcium ion-induced quenching of the intrinsic fluorescence, protection of the N-terminal amino group from acetylation by calcium ions, chemical modification of the N-terminus to a trinitrophenyl derivative, and the possibility of a calcium-binding site(s) in the kringle domain. C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT BIOL,CHAPEL HILL,NC 27599. CRAY RES INC,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. MICHIGAN STATE UNIV,DEPT CHEM,E LANSING,MI 48824. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL-20161, HL-25942, HL-27995] NR 36 TC 26 Z9 26 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 22 PY 1992 VL 31 IS 37 BP 8840 EP 8848 DI 10.1021/bi00152a021 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JP507 UT WOS:A1992JP50700021 PM 1390671 ER PT J AU OMATA, Y FRIEDMAN, FK AF OMATA, Y FRIEDMAN, FK TI CYTOCHROME-P450 BENZPHETAMINE INTERACTIONS IN THE ENDOPLASMIC-RETICULUM - STUDIES USING A MONOCLONAL-ANTIBODY TO P450B SO BIOCHEMISTRY LA English DT Article ID RAT-LIVER CYTOCHROME-P-450; 7-ETHOXYRESORUFIN O-DEETHYLASE; ARYL-HYDROCARBON HYDROXYLASE; MICROSOMAL CYTOCHROME-P-450; SPIN STATE; DIRECTED RADIOIMMUNOASSAY; TEMPERATURE-DEPENDENCE; PROTEIN INTERACTIONS; MEMBRANE TOPOLOGY; PURIFICATION AB A monoclonal antibody (MAb) to phenobarbital-induced rat cytochrome P450b was used to study the interaction of the substrate benzphetamine (Bz) with cytochromes P450 in liver microsomes. Binding of Bz to liver microsomes from phenobarbital-treated rats was monitored by the substrate-induced type I spectral change. The MAb maximally inhibited this spectral change by 49%, providing a probe to distinguish MAb-specific P450b from other Bz-binding P450s. Thermodynamic parameters of the interaction were determined in the absence and presence of MAb. The MAb did not influence the spin-state equilibrium of substrate-free P450b, but it increased the low spin content of substrate-bound P450b. The MAb also decreased the affinity of both high and low spin P450b for Bz. The temperature dependence of the Bz-binding interactions revealed a transition near 20-degrees-C. Fluorescence polarization measurements of the membrane probe 1,6-diphenyl-1,3,5-hexatriene also revealed a transition at this temperature. The MAb comparably inhibited Bz binding to high spin P450b in the low and high temperature regions, whereas MAb inhibition of Bz binding to low spin P450b was greater in the low temperature region than in the high temperature region. These results indicate temperature-dependent changes in membrane structure that modulate both Bz binding to P450b and MAb-P450b-Bz interactions. These results also demonstrate the utility of MAbs for evaluating P450-substrate binding microequilibria of MAb-specific P450s in the presence of other P450s while in the natural membrane environment of the endoplasmic reticulum. C1 NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E-24,BETHESDA,MD 20892. RI Friedman, Fred/D-4208-2016 NR 45 TC 4 Z9 4 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 22 PY 1992 VL 31 IS 37 BP 8862 EP 8867 DI 10.1021/bi00152a024 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JP507 UT WOS:A1992JP50700024 PM 1390673 ER PT J AU GRIBSKOV, M AF GRIBSKOV, M TI TRANSLATIONAL INITIATION FACTOR-IF-1 AND FACTOR-EIF-2-ALPHA SHARE AN RNA-BINDING MOTIF WITH PROKARYOTIC RIBOSOMAL PROTEIN-S1 AND POLYNUCLEOTIDE PHOSPHORYLASE SO GENE LA English DT Note DE PROFILE AND SEQUENCE ANALYSIS; PROTEIN STRUCTURE; HOMOLOGIES ID ESCHERICHIA-COLI; PROFILE ANALYSIS; NUCLEIC-ACID; SEQUENCE; S1; SUBUNIT; DOMAIN; GENE AB Initiation of translation is a complicated process involving numerous accessory factors whose functions remain incompletely understood. Bacterial ribosomal protein S1 is known to contain a repeated sequence motif (S1-RM), also found in polynucleotide phosphorylase, that is thought to be involved in binding to RNA. Using the technique of profile analysis, the S1-RM can also be found in bacterial and chloroplast translation initiation factor IF-1 sequences, and in the sequences of eukaryotic translation initiation factor eIF-2alpha chains. The significance of the similarity of the sequences is very high suggesting that the occurrence of the S1-RM in these diverse proteins represents homology. The similarity of S1 to IF-1 further suggests that S1 has evolved from an IF-1 like ancestor, and therefore that the two proteins have a similar or competitive function. The most obvious common function of the proteins containing the S1-RM seems to be RNA binding, suggesting that IF-1 and eIF-2alpha may bind to RNA. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. FU NCI NIH HHS [N01-CO-74101] NR 14 TC 62 Z9 63 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 21 PY 1992 VL 119 IS 1 BP 107 EP 111 DI 10.1016/0378-1119(92)90073-X PG 5 WC Genetics & Heredity SC Genetics & Heredity GA JP967 UT WOS:A1992JP96700014 PM 1383091 ER PT J AU HAYES, JJ TULLIUS, TD AF HAYES, JJ TULLIUS, TD TI STRUCTURE OF THE TFIIIA 5-S DNA COMPLEX SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DNA PROTEIN COMPLEXES; TRANSCRIPTION FACTOR-IIIA; MISSING-NUCLEOSIDE EXPERIMENT; ZINC FINGER ID TRANSCRIPTION FACTOR-IIIA; 5S RNA GENE; INTERNAL CONTROL REGION; ZINC-BINDING DOMAINS; XENOPUS 5S-RNA GENE; PROTEIN; RECOGNITION; CONTACTS; MODEL C1 JOHNS HOPKINS UNIV,DEPT CHEM,BALTIMORE,MD 21218. RP HAYES, JJ (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. RI Tullius, Thomas/A-9685-2008 OI Tullius, Thomas/0000-0003-4425-796X FU NCI NIH HHS [CA 01208]; NIGMS NIH HHS [GM 41930] NR 30 TC 85 Z9 87 U1 1 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 20 PY 1992 VL 227 IS 2 BP 407 EP 417 DI 10.1016/0022-2836(92)90897-S PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JQ373 UT WOS:A1992JQ37300008 PM 1404361 ER PT J AU MELNICK, RL HUFF, J MATANOSKI, GM AF MELNICK, RL HUFF, J MATANOSKI, GM TI CARCINOGENICITY OF 1,3-BUTADIENE SO LANCET LA English DT Letter C1 JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. RP MELNICK, RL (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 9 TC 4 Z9 4 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD SEP 19 PY 1992 VL 340 IS 8821 BP 724 EP 725 DI 10.1016/0140-6736(92)92259-I PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JN780 UT WOS:A1992JN78000025 PM 1355815 ER PT J AU ROTH, DB MENETSKI, JP NAKAJIMA, PB BOSMA, MJ GELLERT, M AF ROTH, DB MENETSKI, JP NAKAJIMA, PB BOSMA, MJ GELLERT, M TI V(D)J RECOMBINATION - BROKEN DNA-MOLECULES WITH COVALENTLY SEALED (HAIRPIN) CODING ENDS IN SCID MOUSE THYMOCYTES SO CELL LA English DT Article ID SITE-SPECIFIC RECOMBINATION; COMBINED IMMUNE-DEFICIENCY; ANTIGEN RECEPTOR GENES; SUPERCOILED DNA; DELTA-GENES; MICE; REARRANGEMENT; MUTATION; PROTEIN; REPAIR AB Lymphoid cells from scid mice initiate V(D)J recombination normally but have a severely reduced ability to join coding segments. Thymocytes from scid mice contain broken DNA molecules at the TCR-delta locus that have coding ends, as well as molecules with signal ends, whereas in normal mice we previously detected only signal ends. Remarkably, these coding (but not signal) ends are sealed into hairpin structures. The formation of hairpins at coding ends may be a universal, early step in V(D)J recombination; this would provide a simple explanation for the origin of P nucleotides in coding joints. These findings may shed light on the mechanism of cleavage and suggest a possible role for the scid factor. C1 FOX CHASE CANC CTR,INST CANC RES,PHILADELPHIA,PA 19111. RP ROTH, DB (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA-04946]; NCRR NIH HHS [RR-05539]; NIAID NIH HHS [AI-13323] NR 35 TC 370 Z9 370 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 18 PY 1992 VL 70 IS 6 BP 983 EP 991 DI 10.1016/0092-8674(92)90248-B PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JN781 UT WOS:A1992JN78100013 PM 1356077 ER PT J AU OK, JH SPENCER, RGS BENNETT, AE GRIFFIN, RG AF OK, JH SPENCER, RGS BENNETT, AE GRIFFIN, RG TI HOMONUCLEAR CORRELATION SPECTROSCOPY IN ROTATING SOLIDS SO CHEMICAL PHYSICS LETTERS LA English DT Article ID NMR AB A two-dimensional homonuclear correlation experiment for magic angle spinning NMR spectroscopy of polycrystalline solids is described. The approach involves application of a multiple pulse mixing period thal scales chemical shifts to zero, thereby removing the barrier to spin exchange among interacting nuclei. Transfer of spin coherence is achieved by a transverse mixing sequence in which eight pi-pulses, pi(x)-pi(x)-pi(y)-pi(y)-pi(-y)-pi(-y)pi(-x)-pi(-x), are applied per rotor period. Spectra of triply-labeled 1,2,3-C-13(3)-D,L-alanine are presented, which demonstrate correlations among all three carbon spins. C1 MIT,FRANCIS BITTER NATL MAGNET LAB,CAMBRIDGE,MA 02139. MIT,DEPT CHEM,CAMBRIDGE,MA 02139. NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 15 TC 39 Z9 39 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD SEP 18 PY 1992 VL 197 IS 4-5 BP 389 EP 395 DI 10.1016/0009-2614(92)85790-H PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA JN548 UT WOS:A1992JN54800009 ER PT J AU EISENLOHR, LC YEWDELL, JW BENNINK, JR AF EISENLOHR, LC YEWDELL, JW BENNINK, JR TI A TRANSIENT TRANSFECTION SYSTEM FOR IDENTIFYING BIOSYNTHESIZED PROTEINS PROCESSED AND PRESENTED TO CLASS-I MHC RESTRICTED LYMPHOCYTES-T SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE CYTOTOXIC LYMPHOCYTE-T; TRANSFECTION; VACCINIA VIRUS; ANTIGEN PRESENTATION; T7 RNA POLYMERASE ID BACTERIOPHAGE-T7 RNA-POLYMERASE; EXPRESSION SYSTEM; VACCINIA VIRUS; INFLUENZA NUCLEOPROTEIN; CELLS; ANTIGEN; RECOGNITION; TRANSLATION; PREDICTION; SEQUENCES AB CD8+ cytotoxic T lymphocytes (CTL) constitute a major portion of immune responses to foreign and self antigens. CTL recognize class I major histocompatibility complex molecules complexed to peptides of 8-10 residues derived from cytosolic proteins. To understand CTL responses to these antigens and to manipulate CTL responses optimally, it is necessary to identify the specific peptides recognized by CTL. The methods currently used for this purpose have significant drawbacks. We describe a plasmid transfection method that results in significant lysis of histocompatible target cells. Influenza virus-specific CTLs specifically lysed target cells that were transfected with plasmids bearing cDNAs encoding full length gene products, fragments containing the region that encodes the CTL epitope, or even a ten residue peptide. This significantly lessens the time and effort required to define genes, and gene segments that contain CTL epitopes. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 30 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD SEP 18 PY 1992 VL 154 IS 1 BP 131 EP 138 DI 10.1016/0022-1759(92)90220-N PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA JP567 UT WOS:A1992JP56700016 PM 1401939 ER PT J AU CARMELLI, D SWAN, GE ROBINETTE, D FABSITZ, R AF CARMELLI, D SWAN, GE ROBINETTE, D FABSITZ, R TI GENETIC INFLUENCE ON SMOKING - A STUDY OF MALE TWINS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CIGARETTE-SMOKING; NICOTINE; PERSPECTIVE; ALCOHOL; STRAINS AB Background. The results of twin and family studies suggest that heredity has a small influence on smoking behavior. Methods. We conducted a genetic analysis of several aspects of smoking behavior among subjects in the National Academy of Sciences-National Research Council Twin Registry. The registry includes male twins who were born in the United States between 1917 and 1927 and who were members of the armed forces during World War II. Information on smoking history was available for 4775 pairs of twins, who were first surveyed in 1967 through 1969, when they were 40 to 50 years old, and then resurveyed in 1983 through 1985, when they were 56 to 66. Eighty percent of the subjects in this cohort had smoked at some time in their lives, 60 percent were smokers in 1967 through 1969, and 39 percent were smoking in 1983 through 1985. Similarities between twins in smoking habits at base line and at the second follow-up 16 years later were examined. The comparison of concordance for smoking between monozygotic and dizygotic twins was used to assess the relative contribution of familial and genetic factors. Results. In the 1967-1969 survey the ratio of observed to expected concordance for smoking was higher among the monozygotic twins than among the dizygotic twins for those who had never smoked (overall rate ratio, 1.38; 95 percent confidence interval, 1.25 to 1.54), for former smokers (overall rate ratio, 1.59; 95 percent confidence interval, 1.35 to 1.85), for current cigarette smokers (overall rate ratio, 1.18; 95 percent confidence interval, 1.11 to 1.26), and for current cigar or pipe smokers (overall rate ratio, 1.60; 95 percent confidence interval, 1.22 to 2.06). The data also suggest genetic influences on quitting smoking. Monozygotic twins were more likely than dizygotic twins to be concordant for quitting smoking (overall rate ratio, 1.24; 95 percent confidence interval, 1.06 to 1.45). Conclusions. In this cohort of adult male twins, there were moderate genetic influences on lifetime smoking practices. C1 NATL ACAD SCI,MED FOLLOW VP AGCY,WASHINGTON,DC 20418. NHLBI,BETHESDA,MD 20892. RP CARMELLI, D (reprint author), SRI INT,HLTH SCI PROGRAM,333 RAVENSWOOD AVE,MENLO PK,CA 94025, USA. FU NHLBI NIH HHS [HL 46115-01]; PHS HHS [4504-9] NR 22 TC 239 Z9 243 U1 0 U2 7 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 17 PY 1992 VL 327 IS 12 BP 829 EP 833 DI 10.1056/NEJM199209173271201 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JN120 UT WOS:A1992JN12000001 PM 1508241 ER PT J AU WARREN, HS DANNER, RL MUNFORD, RS AF WARREN, HS DANNER, RL MUNFORD, RS TI ANTIENDOTOXIN MONOCLONAL-ANTIBODIES - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH,BETHESDA,MD 20205. UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. RP WARREN, HS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 17 PY 1992 VL 327 IS 12 BP 890 EP 890 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JN120 UT WOS:A1992JN12000018 ER PT J AU LIN, AY IHDE, DC AF LIN, AY IHDE, DC TI SCREENING FOR LUNG-CANCER HAS NO PROVEN UTILITY - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID PROGRAM RP LIN, AY (reprint author), NCI,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 16 PY 1992 VL 268 IS 11 BP 1413 EP 1413 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JM849 UT WOS:A1992JM84900018 ER PT J AU LOCKSHIN, MD AF LOCKSHIN, MD TI ANTIPHOSPHOLIPID ANTIBODY SYNDROME SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTICARDIOLIPIN ANTIBODIES; CLINICAL ASPECTS; FETAL DEATH; ANTICOAGULANTS; VASCULOPATHY; MICE RP LOCKSHIN, MD (reprint author), NATL INST ARTHRIT & MUSCULOSKELETAL & SKIN DIS,EXTRAMURAL PROGRAM,BLDG 31,ROOM 4C32,BETHESDA,MD 20892, USA. NR 23 TC 50 Z9 51 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 16 PY 1992 VL 268 IS 11 BP 1451 EP 1453 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA JM849 UT WOS:A1992JM84900030 PM 1512915 ER PT J AU CONE, EJ DEYL, Z AF CONE, EJ DEYL, Z TI TOXICOLOGICAL AND FORENSIC APPLICATIONS OF CHROMATOGRAPHY - FOREWORD SO JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS LA English DT Editorial Material RP CONE, EJ (reprint author), NIDA,ADDICT RES CTR,BALTIMORE,MD 21224, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR-BIOMED JI J. Chromatogr.-Biomed. Appl. PD SEP 16 PY 1992 VL 580 IS 1-2 BP 1 EP 1 DI 10.1016/0378-4347(92)80525-U PG 1 WC Chemistry, Analytical SC Chemistry GA JP568 UT WOS:A1992JP56800001 ER PT J AU CONE, EJ DARWIN, WD AF CONE, EJ DARWIN, WD TI RAPID ASSAY OF COCAINE, OPIATES AND METABOLITES BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY SO JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS LA English DT Review ID ECGONINE METHYL-ESTER; PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; TESTING HUMAN HAIR; POPPY-SEED; HUMAN-URINE; BIOLOGICAL-FLUIDS; SIMULTANEOUS IDENTIFICATION; MAJOR METABOLITE; ILLICIT COCAINE AB The simultaneous assay of cocaine, opiates and metabolites in small biological samples continues to be a difficult task. This report focuses upon tabulation of important techniques (extraction, derivatization, chromatographic conditions, detection mode, data acquisition) reported over the last decade that were used in the development of assays for these analytes. The most prevalent procedures for extraction of cocaine, opiates and metabolites were liquid-liquid and solid-phase extraction isolation methods. Following extraction analytes were derivatized and analyzed by gas chromatography-mass spectrometry. The technique most often used for chromatographic separation was fused-silica capillary column gas chromatography. Detection generally was performed by selected ion monitoring in the positive-ion electron-impact ionization mode, although full-scan acquisition and positive- and negative-ion chemical ionization methods have been used. It was apparent from the review that there is a continuing need for greater sensitivity and selectivity in the assay of highly potent opiates and for cocaine and metabolites. RP CONE, EJ (reprint author), NIDA,ADDICT RES CTR,BALTIMORE,MD 21224, USA. NR 116 TC 29 Z9 29 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR-BIOMED JI J. Chromatogr.-Biomed. Appl. PD SEP 16 PY 1992 VL 580 IS 1-2 BP 43 EP 61 DI 10.1016/0378-4347(92)80527-W PG 19 WC Chemistry, Analytical SC Chemistry GA JP568 UT WOS:A1992JP56800003 PM 1400832 ER PT J AU TARONE, RE CHU, KC AF TARONE, RE CHU, KC TI IMPLICATIONS OF BIRTH COHORT PATTERNS IN INTERPRETING TRENDS IN BREAST-CANCER RATES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TEMPORAL VARIATION; UNITED-STATES; AGE PERIOD; CONNECTICUT; MORTALITY; MODELS AB Background: Most investigations of trends in cancer rates are based on a cross-sectional approach, i.e., an examination of trends in rates by year of diagnosis or death. When there are longitudinal effects (i.e., trends in rates with successive birth cohorts), interpretation of cross-sectional trends can be misleading. Based on cross-sectional comparisons, U.S. breast cancer mortality rates have been reported to be decreasing over the last 20 years in younger women but to be increasing during the same period in older women. Purpose: To examine the impact of longitudinal effects on the divergence of cross-sectional trends in breast cancer mortality with age, we examined breast cancer mortality rates from 1969 to 1988 by birth cohort for White women in the United States. Methods: By using a novel. nonparametric, permutational method to analyze 2-year, age-specific mortality rates for women aged 30-89 years, we identified trends in rates with successive birth cohorts. Results: The divergence in trends with age is shown to be consistent with an increase in breast cancer risk with successive birth cohorts from 1900 to 1916 and with a decrease in breast cancer risk with successive birth cohorts beginning around 1926. Conclusion: Longitudinal effects have a significant impact on cross-sectional trends in breast cancer mortality. Implications: Continuation of the birth cohort trend in younger women, which could correspond to changes in reproductive patterns accompanying the "baby boom," would result in decreasing cross-sectional trends in women 60-69 years of age over the next decade and in women 70-79 years of age in the subsequent decade. Longitudinal effects must be taken into consideration when monitoring and evaluating the effects of early detection, treatment, and intervention programs using national rates. C1 NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,BETHESDA,MD 20892. RP TARONE, RE (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,RM 403,BETHESDA,MD 20892, USA. NR 20 TC 56 Z9 57 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 16 PY 1992 VL 84 IS 18 BP 1402 EP 1410 DI 10.1093/jnci/84.18.1402 PG 9 WC Oncology SC Oncology GA JM871 UT WOS:A1992JM87100010 PM 1512791 ER PT J AU TRAVIS, LB CURTIS, RE HANKEY, BF FRAUMENI, JF AF TRAVIS, LB CURTIS, RE HANKEY, BF FRAUMENI, JF TI 2ND CANCERS IN PATIENTS WITH CHRONIC LYMPHOCYTIC-LEUKEMIA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HODGKINS-DISEASE; MALIGNANT-MELANOMA; BREAST-CANCER; RISK; LYMPHOMA; CYCLOPHOSPHAMIDE; CHLORAMBUCIL; IRRADIATION; MECHANISM; NEOPLASMS AB Background: Reports to date have provided widely divergent estimates of the risk of second malignant neoplasms in patients with chronic lymphocytic leukemia (CLL), ranging from cancer deficits to excesses of twofold to threefold. Purpose: Our purpose was to estimate the risk of second primary cancers following CLL, utilizing population-based tumor registries, and to determine whether site-specific excesses might be associated with type of initial treatment for CLL. Methods: We analyzed data for 9456 patients diagnosed with CLL as a first primary cancer between 1973 and 1988, who were reported to one of nine tumor registries participating in the National Cancer Institute's Surveillance, Epidemiology, and Ene Results (SEER) Program and who survived 2 or more months. SEER files were searched for invasive primary malignancies that developed a least 2 months after the initial CLL diagnosis. Results: Compared with the general population, CLL patients demonstrated a significantly increased risk of developing all second cancers (840 observed: observed-to-expected ratio [O/E] = 1.28; 95% confidence interval [CI] = 1.19-1.37). Significant excesses were noted for cancers of the lung (O/E = 1.90), brain (O/E = 1.98), and eye (intraocular melanoma) (O/E = 3.97) as well as malignant melanoma (O/E = 2.79) and Hodgkin's disease (O/E = 7.69). Cancer risk. which did not vary according to initial treatment category, was also constant across all time intervals after CLL diagnosis. Conclusion: CLL patients are at a significantly increased risk of developing a second malignant neoplasm. The pattern of cancer excesses suggests a susceptibility state permitting the development of selected second malignancies in patients with CLL. perhaps because of shared etiologic factors, immunologic impairment, and/or other influences. Although our results do not suggest a strong treatment effect, more detailed studies of second tumors in CLL are needed to investigate the role of radiation therapy and chemotherapy. C1 NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,CANC STAT BRANCH,BETHESDA,MD 20892. RP TRAVIS, LB (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,STE 408,BETHESDA,MD 20892, USA. NR 51 TC 157 Z9 160 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 16 PY 1992 VL 84 IS 18 BP 1422 EP 1427 DI 10.1093/jnci/84.18.1422 PG 6 WC Oncology SC Oncology GA JM871 UT WOS:A1992JM87100013 PM 1512794 ER PT J AU SOPKO, G ROGERS, WJ ALSHAIBI, K BITNER, V BLACKBURN, G COX, D LEVSON, L MCDANIEL, L MOODY, J MORGAN, T PARKS, M TAYLOR, H VARMA, V PRATT, C FRANCIS, M HABIB, G JOHNSON, S KLEIMAN, N MAHMARIAN, J MORRIS, G ROBERTS, R RODRIGUEZ, R STEIN, B THIBEDEAUX, C SELWYN, AP BARRY, J RABY, K STONE, P VITA, G YOUNG, A PEPINE, CJ ALEXANDER, J BERTOLET, B HANDBERG, E HILL, J KOLB, R LIMACHER, M MEHTA, J RUBY, G GOLDBERG, AD DVORAK, L FRANK, D GOLDSTEIN, S JAFRI, S KNIGHT, K KRAFT, RN OUYANG, P ACHUFF, S BAUGHMAN, K BRINKER, J GOTTLIEB, SO GOTTLIEB, S GROMAN, G KELEMEN, M LUTZ, H SCHULMAN, S TOWNSEND, S MUELLER, H BILODEAU, S COGLIANESE, ME FORNAISERBONGO, M FRISHMAN, W FURIA, S HEMINGWAY, K STEINGART, R VENTURA, B BOURASSA, MG BONAN, R DYRDA, I FAILLE, C LECLERC, Y LESPERANCE, J PELLETIER, C TRUDEL, J WATERS, DD WHITTOM, L DAVIES, RF BAIRD, M BEANLANDS, D BAKER, A FRASER, M GRICHEN, S DEANFIELD, JE DYMOND, D ELSTOB, J CHAITMAN, BR BJERREGAARD, P BYERS, S CARALIS, DG COHEN, J KAISER, G KERN, M MCBRIDE, L MILLER, DD WIENS, RD WILLIAMS, G AF SOPKO, G ROGERS, WJ ALSHAIBI, K BITNER, V BLACKBURN, G COX, D LEVSON, L MCDANIEL, L MOODY, J MORGAN, T PARKS, M TAYLOR, H VARMA, V PRATT, C FRANCIS, M HABIB, G JOHNSON, S KLEIMAN, N MAHMARIAN, J MORRIS, G ROBERTS, R RODRIGUEZ, R STEIN, B THIBEDEAUX, C SELWYN, AP BARRY, J RABY, K STONE, P VITA, G YOUNG, A PEPINE, CJ ALEXANDER, J BERTOLET, B HANDBERG, E HILL, J KOLB, R LIMACHER, M MEHTA, J RUBY, G GOLDBERG, AD DVORAK, L FRANK, D GOLDSTEIN, S JAFRI, S KNIGHT, K KRAFT, RN OUYANG, P ACHUFF, S BAUGHMAN, K BRINKER, J GOTTLIEB, SO GOTTLIEB, S GROMAN, G KELEMEN, M LUTZ, H SCHULMAN, S TOWNSEND, S MUELLER, H BILODEAU, S COGLIANESE, ME FORNAISERBONGO, M FRISHMAN, W FURIA, S HEMINGWAY, K STEINGART, R VENTURA, B BOURASSA, MG BONAN, R DYRDA, I FAILLE, C LECLERC, Y LESPERANCE, J PELLETIER, C TRUDEL, J WATERS, DD WHITTOM, L DAVIES, RF BAIRD, M BEANLANDS, D BAKER, A FRASER, M GRICHEN, S DEANFIELD, JE DYMOND, D ELSTOB, J CHAITMAN, BR BJERREGAARD, P BYERS, S CARALIS, DG COHEN, J KAISER, G KERN, M MCBRIDE, L MILLER, DD WIENS, RD WILLIAMS, G TI ASYMPTOMATIC CARDIAC ISCHEMIA PILOT-STUDY (ACIP) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB Ischemia can lead to myocardial necrosis, arrhythmias and death. Current practice suggests that asymptomatic or silent myocardial ischemia be treated as though it were symptomatic ischemia. This practice is associated with a growing trend of more frequent use of electrocardiographic monitoring, more complex therapeutic drug regimens and more frequent use of revascularization. However, there is no adequate study of the efficacy and safety of alternative therapeutic approaches to the treatment of asymptomatic myocardial ischemia. Therefore, the National Heart, Lung, and Blood Institute has planned the Asymptomatic Cardiac Ischemia Pilot (ACIP) study. The ACIP study is a multicenter international pilot trial to determine the efficacy and safety of angina-directed medical therapy, angina plus ambulatory electrocardiographic-directed medical therapy and revascularization. The treatment of asymptomatic cardiac ischemia is double-blind and placebo-controlled. The primary end point is elimination of ischemia on the 48-hour electrocardiogram at 12 weeks. Patients will be followed-up for at least 1 year. Secondary analyses will include comparisons of the 2 medical regimens, amounts of medicine taken, and exercise versus electrocardiographic results. Eleven clinical units are recruiting 600 patients with coronary anatomy suitable for revascularization, a positive exercise stress test, and 1 or more asymptomatic ischemic episodes on the 48-hours electrocardiogram. Patients are stratified by center, symptom status and previous coronary surgery. If warranted by the pilot study results, a full-scale trial will be considered to determine whether amelioration of asymptomatic ischemia improves survival and reduces cardiovascular morbidity, C1 UNIV ALABAMA,BIRMINGHAM,AL 35294. BAYLOR COLL MED,HOUSTON,TX 77030. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV FLORIDA,GAINESVILLE,FL 32611. VET ADM MED CTR,GAINESVILLE,FL 32602. HENRY FORD HOSP,DETROIT,MI 48202. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. MONTREAL HEART INST,MONTREAL H1T 1C8,QUEBEC,CANADA. UNIV OTTAWA,INST HEART,OTTAWA K1N 6N5,ONTARIO,CANADA. ST BARTHOLOMEWS HOSP,LONDON EC1A 7BE,ENGLAND. ST LOUIS UNIV,ST LOUIS,MO 63103. VET ADM MED CTR,ST LOUIS,MO 63125. RP SOPKO, G (reprint author), NHLBI,DIV HEART & VASC DIS,CARDIAC DIS BRANCH,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. RI Deanfield, John/C-5178-2008 NR 0 TC 14 Z9 14 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 1992 VL 70 IS 7 BP 744 EP 747 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JM228 UT WOS:A1992JM22800008 ER PT J AU FLEG, JL KENNEDY, HL AF FLEG, JL KENNEDY, HL TI LONG-TERM PROGNOSTIC-SIGNIFICANCE OF AMBULATORY ELECTROCARDIOGRAPHIC FINDINGS IN APPARENTLY HEALTHY SUBJECTS-GREATER-THAN-OR-EQUAL-TO-60 YEARS OF AGE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID VENTRICULAR ECTOPIC BEATS; HEART-DISEASE; CARDIAC-CATHETERIZATION; MYOCARDIAL-INFARCTION; SILENT ISCHEMIA; FOLLOW-UP; ARRHYTHMIAS; MORTALITY; POPULATION; COMPLEXES AB To determine the long-term prognostic significance of frequent or complex ectopic beats and ST-segment changes on 24-hour ambulatory electrocardiogram (ECG) in apparently healthy older subjects, 98 volunteers were followed up from the Baltimore Longitudinal Study of Aging who were 60 to 85 years old and free of cardiac disease by history, physical examination and maximal treadmill testing at the time of ambulatory ECG between 1978 and 1980. Over a mean follow-up period of 10 years, coronary events developed in 14 subjects: angina pectoris in 7, nonfatal myocardial infarction in 3 and sudden cardiac death in 4. The incidence of coronary events did not differ significantly between subjects who developed the following arrhythmias and those who did not, respectively: greater-than-or-equal-to 30 supraventricular ectopic beats in any hour, 18 vs 13%; greater-than-or-equal-to 100 supraventricular ectopic beats in 24 hours, 20 vs 12%; paroxysmal atrial tachycardia, 15 vs 14%; greater-than-or-equal-to 30 ventricular ectopic complexes (VECs) in any hour, 17 vs 14%; greater-than-or-equal-to 100 VECs in 24 hours, 18 vs 14%; or repetitive VECs, 20 vs 13%. The mean 24-hour heart rate (75 +/- 8 vs 72 +/- 9 beats/min) as well as the maximal (116 +/- 20 vs 111 +/- 18 beats/min) and minimal (51 +/- 6 vs 53 +/- 7 beats/min) heart rate also did not differ between the coronary event and non-event groups. Although flat or downsloping ST-segment depression greater-than-or-equal-to 1.0 mm was seen in only 5 subjects, coronary events occurred in 2 of these 5 (40%) vs only 12 (13%) of 93 subjects without such ST-segment changes. When 11 additional persons with lesser degrees of ST-segment depression were included, events occurred in 6 of 16 (38%) compared with 8 of 82 (10%) subjects without any ST-segment changes, p <0.05. In 2 of the 3 subjects who died suddenly, both nonsustained ventricular tachycardia and ST-segment depression were present. Thus, neither supraventricular ectopic beats nor simple VEC patterns on ambulatory ECG predict the development of future coronary events in clinically healthy older subjects; ambulant silent ischemia, although infrequent, may be the best predictor of future coronary events in such a population. C1 RUSH PRESBYTERIAN ST LUKES MED CTR,CARDIOL SECT,CHICAGO,IL 60612. RP FLEG, JL (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 19 TC 60 Z9 62 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 1992 VL 70 IS 7 BP 748 EP 751 DI 10.1016/0002-9149(92)90553-B PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JM228 UT WOS:A1992JM22800009 PM 1381549 ER PT J AU MARON, BJ WOLFSON, JK ROBERTS, WC AF MARON, BJ WOLFSON, JK ROBERTS, WC TI RELATION BETWEEN EXTENT OF CARDIAC-MUSCLE CELL DISORGANIZATION AND LEFT-VENTRICULAR WALL THICKNESS IN HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ASYMMETRIC SEPTAL HYPERTROPHY; QUANTITATIVE-ANALYSIS; OBSTRUCTIVE CARDIOMYOPATHY; DISEASE; FIBROSIS AB The presence of numerous, abnormally arranged, cardiac muscle cells distributed widely throughout the hypertrophied left ventricular (LV) wall has been considered a characteristic, morphologic feature of patients dying of hypertrophic cardiomyopathy (HC) and also probably a determinant of impaired LV compliance. However, the relation between such regions of myocardial cell disarray and the magnitude of wall thickness in the same areas of the left ventricle has not been defined. Therefore, the present study was undertaken in which LV wall thickness and the percent area of myocardium disorganized were systematically compared in the same tissue section. No correlation was identified between wall thickness and the amount of myocardium disorganized in the same tissue sections, either when calculated separately for the ventricular septum, and anterolateral and posterior free walls, or when expressed for all 3 regions combined. Therefore, in patients with HC: (1) disorganized myocardial architecture is not confined to greatly thickened portions of the LV wall, but regions of the left ventricle with normal or only mildly increased thickness may also be disordered; and (2) whereas both LV wall thickening and cellular disorganization are manifestations of the primary cardiomyopathic process, these 2 morphologic features do not appear to be directly related with regard to their extent and distribution within the LV wall. These observations will potentially enhance understanding of the relation between LV structure and compliance in HC. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. RP MARON, BJ (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 26 TC 50 Z9 50 U1 1 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 1992 VL 70 IS 7 BP 785 EP 790 DI 10.1016/0002-9149(92)90560-L PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JM228 UT WOS:A1992JM22800016 PM 1519531 ER PT J AU SAGIE, A LARSON, MG GOLDBERG, RJ BENGTSON, JR LEVY, D AF SAGIE, A LARSON, MG GOLDBERG, RJ BENGTSON, JR LEVY, D TI AN IMPROVED METHOD FOR ADJUSTING THE QT INTERVAL FOR HEART-RATE (THE FRAMINGHAM HEART-STUDY) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; SUDDEN-DEATH; CARDIOVASCULAR MORTALITY; LONG QT; PROLONGATION; ELECTROCARDIOGRAM; PREDICTION; DISCHARGE; DURATION; FORMULAS AB Several formulas have been proposed to adjust the QT interval for heart rate, the most commonly used being the QT correction formula (QT(c) = QT/square-root RR) proposed in 1920 by Bazett. The QT(c) formula was derived from observations in only 39 young subjects. Recently, the adequacy of Bazett's formula has been questioned. To evaluate the heart rate QT association, the QT interval was measured on the initial baseline electrocardiogram of 5,018 subjects (2,239 men and 2,779 women) from the Framingham Heart Study with a mean age of 44 years (range 28 to 62). Persons with coronary artery disease were excluded. A linear regression model was developed for correcting QT according to RR cycle length. The large sample allowed for subdivision of the population into sex-specific deciles of RR intervals and for comparison of QT, Bazett's QT(c) and linear corrected QT (QT(LC)). The mean RR interval was 0.81 second (range 0.5 to 1.47) heart rate 74 beats/min (range 41 to 120), and mean QT was 0.35 second (range 0.24 to 0.49) in men and 0.36 second (range 0.26 to 0.48) in women. The linear regression model yielded a correction formula (for a reference RR interval of 1 second): QT(LC) = QT + 0.154 (1 - RR) that applies for men and women. This equation corrects QT more reliably than the Bazett's formula, which overcorrects the QT interval at fast heart rates and undercorrects it at low heart rates. Lower and upper limits of normal QT values in relation to RR were generated. A simple linear equation was developed that is more accurate than Bazett's correction at different cycle lengths and more convenient for clinical practice. This formula alleviates the need to apply secondary corrections to Bazett's formula. Additional investigation is warranted to determined whether QT(LC) improves the identification of subjects at high risk for malignant arrhythmias or sudden death. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,5 THURBER ST,FRAMINGHAM,MA 01701. BOSTON UNIV,SCH MED,DIV EPIDEMIOL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DIV PREVENT MED,BOSTON,MA 02118. UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA 01605. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. NHLBI,BETHESDA,MD 20892. NR 31 TC 382 Z9 391 U1 0 U2 11 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 1992 VL 70 IS 7 BP 797 EP 801 DI 10.1016/0002-9149(92)90562-D PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JM228 UT WOS:A1992JM22800018 PM 1519533 ER PT J AU ALAVANJA, MCR BROWNSON, RC BOICE, JD HOCK, E AF ALAVANJA, MCR BROWNSON, RC BOICE, JD HOCK, E TI PREEXISTING LUNG-DISEASE AND LUNG-CANCER AMONG NONSMOKING WOMEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ADENOCARCINOMA; ASTHMA; EMPHYSEMA; LUNG DISEASES; LUNG NEOPLASMS; PNEUMONIA; TUBERCULOSIS ID OBSTRUCTIVE PULMONARY-DISEASE; RISK-FACTORS; TUBERCULOSIS PATIENTS; FAMILY HISTORY; SMOKING; MORTALITY; ADENOCARCINOMA; ASTHMA; COHORT AB Preexisting lung disease was examined as a risk factor for lung cancer in a population-based, case-control study of nonsmoking women in Missouri conducted between June 1, 1986, and April 1, 1991. A history of lung disease was reported by approximately 41 % of 618 cases and 35% of 1,402 controls (odds ratio (OR) = 1.2; 95% confidence interval (Cl) 1.0-1.5. The risk was more pronounced when next-of-kin interviews were excluded (OR = 1.5). Previous lung disease was significantly related both to adenocarcinoma (OR = 1.4), which accounted for 62% of the cancers, and to all other cell types of lung cancer combined (OR = 1.8). Despite having discontinued smoking for more than 15 years, long-term ex-smokers were at a 2.2-fold risk of lung cancer compared with lifetime nonsmokers. Among lifetime nonsmokers, significant risks were noted for asthma (OR = 2.7) and pneumonia (OR = 1.5). Emphysema (OR = 2.6) and tuberculosis (OR = 2.0) were also significantly related to lung cancer, but only among former smokers. Chronic bronchitis was linked to elevated risks of nonadenocarcinomas only (OR = 2.3). Pleurisy was not reported more frequently by cases than by controls. Approximately 16% of all lung cancers among nonsmoking women could be attributed to previous lung diseases, most notably asthma, pneumonia, emphysema, and tuberculosis. C1 MISSOURI DEPT HLTH,DIV CHRON DIS PREVENT & HLTH PROMOT,COLUMBIA,MO. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD. RP ALAVANJA, MCR (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,EXECUT PLAZA N,ROOM 543,ROCKVILLE,MD 20852, USA. NR 38 TC 126 Z9 126 U1 0 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1992 VL 136 IS 6 BP 623 EP 632 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JY025 UT WOS:A1992JY02500001 PM 1442729 ER PT J AU HOOK, EW REICHART, CA UPCHURCH, DM RAY, P CELENTANO, D QUINN, TC AF HOOK, EW REICHART, CA UPCHURCH, DM RAY, P CELENTANO, D QUINN, TC TI COMPARATIVE BEHAVIORAL EPIDEMIOLOGY OF GONOCOCCAL AND CHLAMYDIAL INFECTIONS AMONG PATIENTS ATTENDING A BALTIMORE, MARYLAND, SEXUALLY-TRANSMITTED DISEASE CLINIC SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CHLAMYDIA; GONORRHEA; SEX BEHAVIOR; SEXUALLY TRANSMITTED DISEASES, BACTERIAL ID TRACHOMATIS; DIAGNOSIS; GONORRHEA; CULTURE AB Between April 1988 and May 1989,400 males and 400 females attending a Baltimore, Maryland, sexually transmitted disease clinic were enrolled in a study evaluating and comparing behaviors associated with culture-proven gonococcal or chlamydial infection. The subjects were enrolled consecutively, and were all seen by the same clinician. Among participants of each sex, gonorrhea but not chlamydia was associated with increasing numbers of recent (the past 30 days) sexual partners. Compared with males with neither infection, factors independently associated with increased risk of gonorrhea included age less than 20 years (odds ratio (OR) = 1.93), the presence of genitourinary symptoms (OR = 8.07), and recent exposure to a new sexual partner (OR = 2.78); risk for chlamydial infection in males was associated with genitourinary symptoms (OR = 2.83) and was significantly reduced in those reporting multiple recent (OR = 0.19) or new (OR = 0.07) sexual partners. Among females, age less than 20 years was independently associated with gonococcal (OR = 1.86) and chlamydial (OR = 7.79) infections in comparison with females with neither infection. No other behavioral factors were associated with chlamydial infection for females in this study; however, having a regular sexual partner was associated with significantly elevated risk of gonorrhea (OR = 3.85), while the presence of genital tract symptoms was associated with diminished risk (OR = 0.29) for gonorrhea. These data suggest that there are differences in the behaviors associated with gonorrheal and chlamydial infections and that different strategies may be useful in efforts to control these infections. C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. BALTIMORE CITY DEPT HLTH,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. NIAID,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-16959] NR 17 TC 46 Z9 46 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1992 VL 136 IS 6 BP 662 EP 672 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JY025 UT WOS:A1992JY02500005 PM 1442733 ER PT J AU LEROITH, D AF LEROITH, D TI OVARIAN INSULIN-LIKE GROWTH-FACTORS - REPLY SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP LEROITH, D (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 15 PY 1992 VL 117 IS 6 BP 535 EP 535 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JN257 UT WOS:A1992JN25700022 ER PT J AU POST, RM WEISS, SRB AF POST, RM WEISS, SRB TI ENDOGENOUS BIOCHEMICAL-ABNORMALITIES IN AFFECTIVE-ILLNESS - THERAPEUTIC VERSUS PATHOGENIC SO BIOLOGICAL PSYCHIATRY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; DIAZEPAM BINDING INHIBITOR; CEREBROSPINAL-FLUID; KINDLED SEIZURES; PSYCHIATRIC-PATIENTS; MESSENGER-RNA; RAT-BRAIN; C-FOS; ELECTROCONVULSIVE-THERAPY; DEPRESSED-PATIENTS AB Examination of the neurobiology of psychiatric illness in general, and of affective disorders in particular, reveals a variety of associated biochemical abnormalities. These have generally been assumed to be part of the pathological process or secondary to it, and thus deserving of therapeutic efforts aimed at reversal. However, recent clinical and preclinical data suggest that some alterations occurring in the affective disorders may be compensatory and adaptive; that is, part of an endogenous therapeutic mechanism rather than part of the evolving disease process. For example, the symptom of sleep loss in depression seems to fall under this rubric inasmuch as sleep deprivation induces mood improvement in depressed patients. Preclinical data are presented that another primary pathological process-the occurrence of kindled seizures-can evoke endogenous compensatory processes that are either anticonvulsant in their own right, or enable the anticonvulsant effects of a drug such as carbamazepine. It may be that some biochemical abnormalities occurring in affective illness are similarly adaptive. As one example, increased thyrotropin-releasing hormone (TRH) has been reported in the cerebrospinal fluid (CSF) of depressed patients. This elevation of TRH and the resulting neuroendocrine profile may be part of an endogenous counter-regulatory process aimed at mood improvement. Again, preclinical seizure models are supportive in that TRH not only is induced following repeated seizures, but also exerts anticonvulsant effects on these same seizures. In an analogous fashion, TRH elevations in depressed patients may also exert ameliorating effects on depressive symptomatology. This formulation presents directly testable hypotheses that could importantly impact on our understanding of the pathophysiology of affective disorders, and suggests novel therapeutic strategies through the enhancement of endogenous compensatory mechanisms. RP POST, RM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,BETHESDA,MD 20892, USA. NR 92 TC 57 Z9 57 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 1992 VL 32 IS 6 BP 469 EP 484 DI 10.1016/0006-3223(92)90216-M PG 16 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KD222 UT WOS:A1992KD22200002 PM 1445965 ER PT J AU MURPHY, WJ TSARFATY, G LONGO, DL AF MURPHY, WJ TSARFATY, G LONGO, DL TI GROWTH-HORMONE EXERTS HEMATOPOIETIC GROWTH-PROMOTING EFFECTS INVIVO AND PARTIALLY COUNTERACTS THE MYELOSUPPRESSIVE EFFECTS OF AZIDOTHYMIDINE SO BLOOD LA English DT Article ID AIDS-RELATED COMPLEX; FACTOR-I; IMMUNE-DEFICIENCY; SUPEROXIDE ANION; SOMATOMEDIN-C; SECRETION; RECEPTOR RP MURPHY, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 567,FREDERICK,MD 21702, USA. NR 18 TC 51 Z9 53 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1992 VL 80 IS 6 BP 1443 EP 1447 PG 5 WC Hematology SC Hematology GA JN507 UT WOS:A1992JN50700010 PM 1520871 ER PT J AU MACINTYRE, EA SMIT, L RITZ, J KIRSCH, IR STROMINGER, JL AF MACINTYRE, EA SMIT, L RITZ, J KIRSCH, IR STROMINGER, JL TI DISRUPTION OF THE SCL LOCUS IN T-LYMPHOID MALIGNANCIES CORRELATES WITH COMMITMENT TO THE T-CELL RECEPTOR-ALPHA-BETA LINEAGE SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; SITE-SPECIFIC RECOMBINATION; LOOP-HELIX PROTEINS; TRANSCRIPTIONAL ENHANCER; GAMMA-DELTA; CHROMOSOMAL TRANSLOCATION; DNA-BINDING; TAL-1 GENE; CHAIN GENE; C-ALPHA C1 USN,MED ONCOL BRANCH,NCI,BETHESDA,MD 20814. HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA47554] NR 51 TC 58 Z9 59 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1992 VL 80 IS 6 BP 1511 EP 1520 PG 10 WC Hematology SC Hematology GA JN507 UT WOS:A1992JN50700019 PM 1387813 ER PT J AU SAMID, D YEH, A PRASANNA, P AF SAMID, D YEH, A PRASANNA, P TI INDUCTION OF ERYTHROID-DIFFERENTIATION AND FETAL HEMOGLOBIN PRODUCTION IN HUMAN LEUKEMIC-CELLS TREATED WITH PHENYLACETATE SO BLOOD LA English DT Article ID PHARMACOLOGICAL MANIPULATION; HYDROXYUREA; ANEMIA; ERYTHROPOIETIN; 5-AZACYTIDINE; 5-AZA-2'-DEOXYCYTIDINE; TRANSFORMATION; ONCOGENES; DISEASE; THERAPY C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. RP SAMID, D (reprint author), NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10,RM 12C103,BETHESDA,MD 20892, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 34 TC 99 Z9 100 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1992 VL 80 IS 6 BP 1576 EP 1581 PG 6 WC Hematology SC Hematology GA JN507 UT WOS:A1992JN50700027 PM 1381630 ER PT J AU HENSON, DE ALBORESSAAVEDRA, J CORLE, D AF HENSON, DE ALBORESSAAVEDRA, J CORLE, D TI CARCINOMA OF THE GALLBLADDER - HISTOLOGIC TYPES, STAGE OF DISEASE, GRADE, AND SURVIVAL RATES SO CANCER LA English DT Article DE CANCER; GALLBLADDER; HISTOLOGIC TYPE; SURVIVAL; STAGE ID BILIARY-TRACT; PROGNOSIS; CANCER; BILE AB Data on patients with gallbladder cancer listed in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were reviewed. Between 1977 and 1986, 3038 patients were recorded in the Program. Histologic grade, histologic type, stage of disease, and vascular invasion were correlated with outcome. Compared with all other histologic types of cancer, papillary carcinomas had the most favorable prognosis. The 2-year survival rate for patients with papillary carcinoma was 47%. A correlation with survival existed between grade, stage of disease, and vascular invasion. The study confirmed that cancers of the gallbladder occur more often in older age groups and are more common in women. Almost 40% of cases are found at an advanced stage. For patients whose enolase tumor was limited to the gallbladder at the time of surgery, the 2-year survival rate was 45% and the 5-year rate was 32%. C1 UNIV TEXAS,HLTH SCI CTR,SW MED SCH,DEPT PATHOL,DALLAS,TX 75235. RP HENSON, DE (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,EPN BLDG,ROOM 305,BETHESDA,MD 20892, USA. NR 25 TC 245 Z9 257 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 1992 VL 70 IS 6 BP 1493 EP 1497 DI 10.1002/1097-0142(19920915)70:6<1493::AID-CNCR2820700608>3.0.CO;2-U PG 5 WC Oncology SC Oncology GA JN875 UT WOS:A1992JN87500007 PM 1516000 ER PT J AU HENSON, DE ALBORESSAAVEDRA, J CORLE, D AF HENSON, DE ALBORESSAAVEDRA, J CORLE, D TI CARCINOMA OF THE EXTRAHEPATIC BILE-DUCTS - HISTOLOGIC TYPES, STAGE OF DISEASE, GRADE, AND SURVIVAL RATES SO CANCER LA English DT Article DE CANCER; EXTRAHEPATIC BILE DUCTS; HISTOLOGIC TYPE; SURVIVAL ID ULCERATIVE-COLITIS; BILIARY TREE; GALLBLADDER AB Data on patients with extrahepatic bile duct carcinomas recorded in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were reviewed. We analyzed the records of 1766 patients reported during a 10-year period (1977-1986). These tumors occurred primarily in older age groups and were slightly more common in males. Histologic grade, histologic types, and stage of disease are useful prognostic indicators. The 5-year survival rate for patients with Stage I disease was 11%. Although carcinomas of the extrahepatic bile ducts are better differentiated than carcinomas arising in the gallbladder, they have a less favorable prognosis. C1 UNIV TEXAS,HLTH SCI CTR,SW MED SCH,DEPT PATHOL,DALLAS,TX 75235. RP HENSON, DE (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,EPN BLDG,ROOM 305,BETHESDA,MD 20892, USA. NR 17 TC 114 Z9 117 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 1992 VL 70 IS 6 BP 1498 EP 1501 DI 10.1002/1097-0142(19920915)70:6<1498::AID-CNCR2820700609>3.0.CO;2-C PG 4 WC Oncology SC Oncology GA JN875 UT WOS:A1992JN87500008 PM 1516001 ER PT J AU SREENATH, T MATRISIAN, LM STETLERSTEVENSON, W GATTONICELLI, S POZZATTI, RO AF SREENATH, T MATRISIAN, LM STETLERSTEVENSON, W GATTONICELLI, S POZZATTI, RO TI EXPRESSION OF MATRIX METALLOPROTEINASE GENES IN TRANSFORMED RAT-CELL LINES OF HIGH AND LOW METASTATIC POTENTIAL SO CANCER RESEARCH LA English DT Article ID BASEMENT-MEMBRANE COLLAGEN; ADENOVIRUS-2 E1A PRODUCTS; EXTRACELLULAR-MATRIX; TISSUE INHIBITOR; IV COLLAGENASE; TUMOR INVASION; MESSENGER-RNA; DEGRADING METALLOPROTEINASES; SYNOVIAL FIBROBLASTS; ENHANCER ELEMENTS AB The enzymes that comprise the family of matrix metalloproteinases (MMPs) share the capacity to degrade extracellular matrix components. A large body of evidence indicates that certain members of this metalloproteinase gene family play critical roles in determining the malignant phenotype of solid tumors. We previously have derived transformed cell lines with vastly different metastatic potentials by transfecting different combinations of oncogenes into primary rat embryo cells. Conditioned medium from those cell lines was assayed by Western blot analysis for the production of four separate matrix metalloproteinases to see whether a correlation could be found between protease expression and the metastatic phenotype. The transformed rat embryo cell lines with high metastatic potential were found to produce high levels of the stromelysin 1 (MMP-3) and stromelysin 2 (MMP-10) proteases, while the nonmetastatic lines produced low or undetectable levels of these two enzymes. No correlation was seen between the metastatic phenotype of the cell lines and the level of expression of two other matrix metalloproteinases, the M(r) 72,000 type IV collagenase (MMP-2) and the M(r) 92,000 gelatinase (MMP-9). These data suggest that the differential regulation of the stromelysin proteases may contribute to the difference seen in the metastatic potential of these cell lines. C1 NCI,PATHOL LAB,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. VANDERBILT UNIV,MED CTR,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37232. NEW ENGLAND MED CTR,DEPT RADIAT ONCOL,BOSTON,MA 02111. AMER RED CROSS,JEROME H HOLLAND LAB,VIROL LAB,ROCKVILLE,MD 20855. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [R29 CA52140-02] NR 63 TC 107 Z9 108 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1992 VL 52 IS 18 BP 4942 EP 4947 PG 6 WC Oncology SC Oncology GA JN053 UT WOS:A1992JN05300014 PM 1325287 ER PT J AU MERWIN, JR LYNCH, MJ MADRI, JA PASTAN, I SIEGALL, CB AF MERWIN, JR LYNCH, MJ MADRI, JA PASTAN, I SIEGALL, CB TI ACIDIC FIBROBLAST GROWTH FACTOR-PSEUDOMONAS EXOTOXIN CHIMERIC PROTEIN ELICITS ANTIANGIOGENIC EFFECTS ON ENDOTHELIAL-CELLS SO CANCER RESEARCH LA English DT Article ID SMOOTH-MUSCLE CELLS; EXTRACELLULAR-MATRIX; PHENOTYPIC MODULATION; TUMOR ANGIOGENESIS; ORGANIZATION; INHIBITION; THERAPY; TOXINS; CANCER AB It has recently been shown that chimeric toxins composed of acidic fibroblast growth factor fused to mutant forms of Pseudomonas exotoxin (aFGF-PE) are cytotoxic to a variety of tumor cell lines with FGF receptors. Although aFGF-PE might be considered as a possible chemotherapeutic toxin, limited knowledge is available concerning its effect on endothelia. This study investigates whether one of the aFGF-PE fusion proteins, aFGF-PE66(4Glu)KDEL, can function as an anti-angiogenic agent. Protein synthesis studies using rat epididymal fat pad microvascular endothelial cells (RFCs) indicated that after 24 h in culture, aFGF-PE had a significant inhibitory effect on protein synthesis at concentrations >100 ng/ml. In cultures incubated with 1000 ng/ml aFGF-PE, RFC protein synthesis was inhibited as much as 83%. RFCs were also cultured in a 3-dimensional type I collagen gel and incubated with either transforming growth factor beta-1, aFGF-PE, or a combination of both. Transforming growth factor beta-1 elicits in vitro angiogenesis in these 3-dimensional cultures which consist of rapid formation of complex tubular structures. Transforming growth factor beta-1-treated RFCs incubated with aFGF-PE were unable to produce this angiogenic response, nor were they able to migrate out of the 3-dimensional culture to form a monolayer as shown by controls. Cell viability analyses showed that aFGF-PE produced a dose-dependent toxic effect which ranged from 10 to 90% cell death. Competition assays in which the chimeric toxin was preincubated with antibodies to aFGF resulted in an 89% reversal of the inhibitory effects of aFGF-PE on endothelial cells. Acidic FGF-PE with a mutation in the ADP ribosylation domain of PE was inactive in both 2-dimensional and 3-dimensional cultures. These data show that aFGF-PE has specific in vitro cytotoxic, antiangiogenic, and antimigratory effects on microvascular endothelia. C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,MOLEC & CELLULAR BIOL,WALLINGFORD,CT. YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06510. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 28 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1992 VL 52 IS 18 BP 4995 EP 5001 PG 7 WC Oncology SC Oncology GA JN053 UT WOS:A1992JN05300023 PM 1381275 ER PT J AU SHAO, ZM SHEIKH, MS ORDONEZ, JV FENG, P KUTE, T CHEN, JC AISNER, S SCHNAPER, L LEROITH, D ROBERTS, CT FONTANA, J AF SHAO, ZM SHEIKH, MS ORDONEZ, JV FENG, P KUTE, T CHEN, JC AISNER, S SCHNAPER, L LEROITH, D ROBERTS, CT FONTANA, J TI IGFBP-3 GENE-EXPRESSION AND ESTROGEN-RECEPTOR STATUS IN HUMAN BREAST-CARCINOMA SO CANCER RESEARCH LA English DT Note ID FACTOR BINDING-PROTEINS; GROWTH FACTOR-I; IGF-I; CANCER; FIBROBLASTS; SECRETION AB Insulin-like growth factors (IGF) I and II are potent mitogens for breast carcinoma proliferation. IGF-mediated proliferative activity can be markedly enhanced by the presence of specific IGF-binding proteins (IGFBPs). IGFBP-3 has been shown to enhance IGF-mediated growth in a number of systems. Studies have demonstrated IGFBP-3 secretion only in estrogen receptor (ER)-negative breast carcinoma cell lines while IGFBP-3 could not be detected in media conditioned by ER-positive cell lines. We investigated whether a relationship exists between ER status and IGFBP-3 mRNA expression in human breast carcinoma biopsy specimens. We have detected IGFBP-3 mRNA in breast carcinoma tissue obtained from patients utilizing in situ hybridization. Quantitation of IGFBP-3 mRNA levels was performed utilizing image cytometry. There was a significantly higher expression of IGFBP-3 mRNA in ER-negative breast carcinoma specimens when compared to the ER-positive specimens. Whether this higher expression of IGFBP-3 mRNA and presumed secretion of IGFBP-3 by ER-negative tumors play a role in the rapid proliferation and poor prognosis of these tumors remains to be determined. C1 UNIV MARYLAND,CTR CANC,RM S9D05,22 S GREENE ST,BALTIMORE,MD 21201. VET ADM MED CTR,BALTIMORE,MD 21286. BOWMAN GRAY MED CTR,DEPT PATHOL,WINSTON SALEM,NC 27157. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT MED,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT SURG,BALTIMORE,MD 21201. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. OI Fontana, Joseph/0000-0003-3829-3358 NR 19 TC 37 Z9 38 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1992 VL 52 IS 18 BP 5100 EP 5103 PG 4 WC Oncology SC Oncology GA JN053 UT WOS:A1992JN05300041 PM 1381277 ER PT J AU HOTH, DF MYERS, MW STEIN, DS AF HOTH, DF MYERS, MW STEIN, DS TI CURRENT STATUS OF HIV THERAPY .1. ANTIRETROVIRAL AGENTS SO HOSPITAL PRACTICE LA English DT Article AB The clinician's armamentarium is no longer limited to zidovudine as the only antiretroviral agent that enhances both quality and length of life. ddI has shown clinical benefit in patients previously treated with zidovudine. Recently, the combination of zidovudine and ddC has been approved on the basis of surrogate marker activity; its clinical role awaits results of ongoing trials. RP HOTH, DF (reprint author), NIAID,TREATMENT RES PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD SEP 15 PY 1992 VL 27 IS 9 BP 145 EP 156 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA JP285 UT WOS:A1992JP28500013 PM 1381716 ER PT J AU KUNKEL, TA AF KUNKEL, TA TI DNA-REPLICATION FIDELITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYMERASE-III HOLOENZYME; 5' EXONUCLEASE ACTIVITY; I KLENOW FRAGMENT; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; KINETIC MECHANISM; MUTATIONAL SPECIFICITY; INVITRO REPLICATION; ERRORS; GENE RP KUNKEL, TA (reprint author), NIEHS, MOLEC GENET LAB, RES TRIANGLE PK, NC 27709 USA. NR 62 TC 166 Z9 169 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 1992 VL 267 IS 26 BP 18251 EP 18254 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JN502 UT WOS:A1992JN50200001 PM 1526964 ER PT J AU BIRD, GS OBIE, JF PUTNEY, JW AF BIRD, GS OBIE, JF PUTNEY, JW TI FUNCTIONAL HOMOGENEITY OF THE NONMITOCHONDRIAL CA2+ POOL IN INTACT MOUSE LACRIMAL ACINAR-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SENSITIVE CALCIUM POOL; INOSITOL 1,4,5-TRISPHOSPHATE; ENDOPLASMIC-RETICULUM; EXOCRINE PANCREAS; NONMUSCLE CELLS; CA-2+ RELEASE; 2ND MESSENGER; HEPATOCYTES; TRISPHOSPHATE; OSCILLATIONS AB In the absence of extracellular Ca2+, treatment of mouse lacrimal acinar cells with maximal concentrations of methacholine released Ca2+ from intracellular stores. No additional Ca2+ was mobilized by subsequent application of the intracellular Ca2+-ATPase inhibitor, thapsigargin, the stable inositol 1,4,5-trisphosphate ((1,4,5)IP3) analog, inositol 2,4,5-trisphosphate ((2,4,5)IP3) (by microinjection), or the Ca2+ ionophore, ionomycin. However, following prolonged activation of cells by methacholine in the presence of extracellular Ca2+, Ca2+ accumulated into a pool which was released by ionomycin but not by thapsigargin. This latter accumulation was blocked by prior microinjection of ruthenium red, indicating that it represents mitochondrial uptake. In saponin-permeabilized lacrimal cells, two Ca2+-sequestering pools were detected: (i) a ruthenium red-sensitive, thapsigargin-insensitive pool, presumed to be the mitochondria; and (ii) a ruthenium red-insensitive, thapsigargin-sensitive pool. Only the thapsigargin-sensitive pool accumulated Ca2+ at concentrations similar to those in unstimulated cells. The thapsigargin-sensitive Ca2+ pool was sensitive to (1,4,5)IP3; however, in contrast to findings in intact cells, only 44% of this pool was releasable by (1,4,5)IP3 or (2,4,5)IP3. These data indicate that, in intact lacrimal acinar cells, all exchangeable (ionomycin-sensitive) Ca2+ resides in a pool which responds homogeneously to agonists, (1,4,5)IP3, and thapsigargin. Prolonged elevation of [Ca2+]i results in Ca2+ accumulation into a second, ruthenium red-sensitive pool, presumably mitochondria. Finally, permeabilization of the cells fragments the non-mitochondrial pool, resulting in two pools, one sensitive and one insensitive to (1,4,5)IP3. RP NIEHS, CELLULAR & MOLEC PHARMACOL LAB, CALCIUM REGULAT SECT, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 32 TC 42 Z9 43 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 1992 VL 267 IS 26 BP 18382 EP 18386 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JN502 UT WOS:A1992JN50200025 PM 1382054 ER PT J AU BACKLUND, PS AF BACKLUND, PS TI GTP-STIMULATED CARBOXYL METHYLATION OF A SOLUBLE FORM OF THE GTP-BINDING PROTEIN G25K IN BRAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C-TERMINAL CYSTEINE; GAMMA SUBUNITS CONTAIN; MEMBRANE-BINDING; BOVINE BRAIN; SACCHAROMYCES-CEREVISIAE; MOLECULAR-CLONING; HUMAN HOMOLOG; LAMIN-B; GENE; IDENTIFICATION AB The GTP-stimulated carboxyl methylation of an M(r) 23,000 protein was investigated in brain homogenates. An M(r) 23,000 methylation substrate was purified from brain homogenates, using an assay for protein methyl-acceptor activity in the presence of a membrane-bound methyltransferase. The M(r) 23,000 methyl-acceptor protein was identified as a soluble form of the GTP-binding protein G25K, based on antibody reactivity and amino acid sequences of tryptic peptides. Two forms of methylated G25K, differing in isoelectric points, were isolated. The soluble G25K could be methylated with a stoichiometry approaching 1 mol of methyl group per mol of G25K, and guanosine 5'-O-3(thio)triphosphate stimulated the methylation by decreasing the K(m) for G25K from 0.79 to 0.17-mu-m. After methylation, the G25K was associated with the membrane fraction. The soluble G25K was isolated as a heterodimer of G25K and an M(r) 28,000 protein. The G25K and M(r) 28,000 protein complex was dissociated with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate detergent, and the subunits were separated by Mono-Q chromatography. The association of the M(r) 28,000 protein with G25K decreased the methylation of G25K and altered the guanine nucleotide specificity, indicating that the M(r) 28,000 protein may regulate the methylation of G25K. RP BACKLUND, PS (reprint author), NIMH,GEN & COMPARAT BIOCHEM LAB,BLDG 36,RM 3D-06,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 46 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 1992 VL 267 IS 26 BP 18432 EP 18439 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JN502 UT WOS:A1992JN50200033 PM 1526984 ER PT J AU HELFERT, RH JUIZ, JM BLEDSOE, SC BONNEAU, JM WENTHOLD, RJ ALTSCHULER, RA AF HELFERT, RH JUIZ, JM BLEDSOE, SC BONNEAU, JM WENTHOLD, RJ ALTSCHULER, RA TI PATTERNS OF GLUTAMATE, GLYCINE, AND GABA IMMUNOLABELING IN 4 SYNAPTIC TERMINAL CLASSES IN THE LATERAL SUPERIOR OLIVE OF THE GUINEA-PIG SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE AMINO ACID NEUROTRANSMITTERS; COLOCALIZATION OF NEUROTRANSMITTERS; SYNAPTIC ORGANIZATION; AUDITORY SYSTEM; SUPERIOR OLIVARY COMPLEX; IMMUNOCYTOCHEMISTRY ID VENTRAL COCHLEAR NUCLEUS; CENTRAL-NERVOUS-SYSTEM; STEM AUDITORY NUCLEI; D-ASPARTIC ACID; BRAIN-STEM; INFERIOR COLLICULUS; TRAPEZOID BODY; IMMUNOCYTOCHEMICAL LOCALIZATION; HORSERADISH-PEROXIDASE; DESCENDING PROJECTIONS AB The goal of this study was to correlate synaptic ultrastructure with transmitter specificity and function in the lateral superior olive (LSO), a nucleus that is thought to play a major role in sound localization. This was accomplished by means of postembedding immunogold immunocytochemistry. Four classes of synaptic terminals were identified in the LSO. They were distinguishable from one another both morphologically and on the basis of their different patterns of immunolabeling for glutamate, glycine, and gamma-aminobutyric acid (GABA). The highest level of glutamate immunoreactivity was found in terminals that contained round vesicles (R) and formed synaptic contacts with asymmetric synaptic junctions. Round-vesicle terminals predominated on small caliber dendrites by a ratio of at least 2:1 over the other classes combined. The thinnest dendrites were typically contacted by R terminals only. The ratio of R terminals to the other types decreased as the caliber of the dendritic profiles they apposed increased so that on the soma, R terminals were outnumbered by at least 2:1 by the other types. Terminals containing flattened vesicles (F) exhibited intense immunoreactivity for both glycine and glutamate, although the glutamate immunolabeling was not as high as that in the R terminals. Flattened-vesicle terminals formed symmetric synaptic contacts with their targets and their distribution was the reverse of that described for R terminals; i.e., they were most abundant on LSO perikarya and fewest on small caliber dendrites. Two terminal types, both containing pleomorphic vesicles and forming symmetric synaptic junctions, were found in far fewer numbers. One group contained large pleomorphic vesicles (LP) and was immunoreactive for both glycine and GABA. The other group contained small pleomorphic vesicles (SP) along with a few dense-core vesicles and labeled for GABA only. The LP terminals were preferentially distributed on somata and large-caliber dendrites, while the SP terminals most often contacted smaller dendrites. Previous work suggests that a large percentage of the R terminals arise from spherical cells in the ipsilateral cochlear nucleus and are excitatory in action. This pathway may use glutamate as a transmitter. Many of the F terminals are thought to originate from the ipsilateral medial nucleus of the trapezoid body and appear to be the inhibitory (glycinergic) terminals from a pathway that originates from the contralateral ear. The origins and functions of LP and SP terminals are unknown, but a few possibilities are discussed along with the significance of cocontainment of neuroactive substances in specific terminal types. C1 UNIV MICHIGAN,KRESGE HEARING RES INST,ANN ARBOR,MI 48109. NIDCD,MOLEC OTOL LAB,BETHESDA,MD 20205. RI juiz, jose/G-3025-2015 OI juiz, jose/0000-0002-9668-8983 FU NINDS NIH HHS [NS-05785, NS-07106, NS-24369] NR 115 TC 87 Z9 88 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 15 PY 1992 VL 323 IS 3 BP 305 EP 325 DI 10.1002/cne.903230302 PG 21 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA JN020 UT WOS:A1992JN02000001 PM 1360986 ER PT J AU CODIAS, EK FLEMING, TJ ZACHARCHUK, CM ASHWELL, JD MALEK, TR AF CODIAS, EK FLEMING, TJ ZACHARCHUK, CM ASHWELL, JD MALEK, TR TI ROLE OF LY-6A/E AND T-CELL RECEPTOR-ZETA FOR IL-2 PRODUCTION PHOSPHATIDYLINOSITOL-ANCHORED LY-6A/E ANTAGONIZES T-CELL RECEPTOR-MEDIATED IL-2 PRODUCTION BY A ZETA-INDEPENDENT PATHWAY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; ANTIGEN RECEPTOR; ACTIVATION; CHAIN; EXPRESSION; MOLECULES; SPECIFICITY; INDUCTION; SUBUNIT AB Ly-6A/E molecules were originally implicated in regulation of T cell activation because anti-Ly-6A/E mAb induce IL-2 production. More recently we have shown that anti-Ly-6A/E also inhibits IL-2 production induced by anti-CD3. In the present study we used mutant and transfected cell lines that varied in expression of Ly-6A/E or TCR-zeta to test whether the positive and negative modulations of IL-2 production by anti-Ly-6A/E occur by distinct mechanisms. Anti-Ly-6A/E inhibited anti-CD3-induced IL-2 production for Ly-6E. 1 -transfected EL4J cells, but did not affect IL-2 production of the parental Ly-6A/E-negative EL4J cells. These results indicate that TCR-mediated IL-2 production can occur in the absence of Ly-6A/E expression and establish that anti-Ly-6A/E-induced inhibition of IL-2 production was the result of antibody binding to Ly-6A/E. As expected, MA5.8 (zeta-negative) or CT108 (zeta-truncated) variants of the 2B4.11 T cell hybridoma did not produce IL-2 when stimulated with anti-Thy-1 or anti-Ly-6A/E mAb. In contrast, anti-Ly-6A/E inhibited anti-CD3-induced IL-2 production by MA5.8 and CT108. Furthermore, anti-Ly-6A/E-induced IL-2 production was restored for zeta-transfected MA5.8. Thus, although induction of IL-2 by anti-Ly-6A/E depends on zeta-expression, inhibition of IL-2 by anti-Ly-6A/E occurs by a zeta-independent mechanism. Interestingly, anti-Ly-6A/E, but not anti-Thy-1, inhibited anti-CD3-induced IL-2 production by MA5.8 and Ly-6E.1-transfected EL4J. Therefore, inhibition of IL-2 production by anti-Ly-6A/E was not a general property of a mAb binding to a phosphatidylinositol-linked molecule, as has been suggested for induction of IL-2 production. Taken together these data suggest that the molecular mechanisms of induction and inhibition of IL-2 production by anti-Ly-6A/E are separable and expression of TCR-zeta is one variable that distinguishes these two pathways. C1 UNIV MIAMI,SCH MED,DEPT MICROBIOL & IMMUNOLOGY R-138,MIAMI,FL 33101. NCI,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. FU NCI NIH HHS [CA 46096] NR 39 TC 23 Z9 23 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1992 VL 149 IS 6 BP 1825 EP 1832 PG 8 WC Immunology SC Immunology GA JN121 UT WOS:A1992JN12100001 PM 1387661 ER PT J AU EGERTON, M BURGESS, WH CHEN, D DRUKER, BJ BRETSCHER, A SAMELSON, LE AF EGERTON, M BURGESS, WH CHEN, D DRUKER, BJ BRETSCHER, A SAMELSON, LE TI IDENTIFICATION OF EZRIN AS AN 81-KDA TYROSINE-PHOSPHORYLATED PROTEIN IN T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN RECEPTOR; PHOSPHOLIPASE C-GAMMA-1; KINASE SUBSTRATE; LPR/LPR MICE; ZETA-CHAIN; ACTIVATION; FAMILY; STIMULATION; PHOSPHATASE; BAND-4.1 AB We have used APT affinity purification to isolate tyrosine-phosphorylated proteins from MRL lpr/lpr (lpr) mouse T cells. One such protein is pp81 ezrin, previously identified as a tyrosine-phosphorylated protein in epidermal growth factor-stimulated A431 carcinoma cells. Biochemical analyses in A431 and gastric parietal cells have revealed ezrin to be a cytoskeleton-associated cytosolic protein. In Jurkat T cells, however, using similar methods we have shown ezrin to be a cytosolic protein with no measurable cytoskeletal association. We also observed no increases in ezrin tyrosine phosphorylation in TCR-stimulated Jurkat T cells, unless the cells were pretreated with protein tyrosine phosphatase inhibitors, suggesting that T cell ezrin tyrosine phosphorylation is tightly controlled by protein tyrosine phosphatases. The fraction of tyrosine phosphorylated ezrin in lpr T cells was 5 to 10 times that observed in Jurkat T cells, which along with constitutive TCR-zeta phosphorylation and pp60fyn over-expression, is a feature of the lpr defect. C1 AMER RED CROSS LABS,ROCKVILLE,MD 20855. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. CORNELL UNIV,BIOCHEM MOLEC & CELL BIOL SECT,ITHACA,NY 14853. RP EGERTON, M (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 36 TC 77 Z9 78 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1992 VL 149 IS 6 BP 1847 EP 1852 PG 6 WC Immunology SC Immunology GA JN121 UT WOS:A1992JN12100004 PM 1381389 ER PT J AU PARKER, KC DIBRINO, M HULL, L COLIGAN, JE AF PARKER, KC DIBRINO, M HULL, L COLIGAN, JE TI THE BETA-2-MICROGLOBULIN DISSOCIATION RATE IS AN ACCURATE MEASURE OF THE STABILITY OF MHC CLASS-I HETEROTRIMERS AND DEPENDS ON WHICH PEPTIDE IS BOUND SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; HISTOCOMPATIBILITY COMPLEX-MOLECULES; SELF-PEPTIDES; HEAVY-CHAIN; SYNTHETIC PEPTIDES; ANTIGEN HLA-A2; VIRAL PEPTIDES; MATRIX PEPTIDE; BINDING-SITE; RECOGNITION AB Stable, recombinant, water-soluble complexes of HLA-A2 and HLA-B27 were reconstituted from I-125-labeled beta-2-microglobulin (beta-2m), a synthetic peptide, and HLA H chain fragments expressed as inclusion bodies in the Escherichia coli cytoplasm. Using this system, we were able to show: 1) the t1/2 of beta-2m dissociation from HLA complexes at 37-degrees-C varied from approximately 40 h to less than 1 h, depending on the peptide employed for reconstitution. Peptide length and composition were found to be critical factors in determining the beta-2m dissociation rate. Endogenous peptides form complexes that are about as stable as those formed with typical antigenic peptides. 2) Peptide exchange reactions, in which an exogenous peptide replaces the peptide that is already bound by the class I molecule, proceed readily for complexes that have rapid beta-2m dissociation rates. Thus, difficulties in demonstrating peptide binding to complexes that contain endogenous peptides can be attributed to the stability of the endogenous peptide/class I molecule complex. 3) The peptide exchange reaction does not require concomitant beta-2m dissociation. 4) Distal parts of the class I molecule, which are not directly involved in peptide binding or beta-2m binding, have a major impact on the stability of class I molecules. Thus, these studies show that the dissociation rate of beta-2m is an excellent measure of how tightly a given peptide binds to class I MHC molecules, that the ability to bind peptide is tightly coupled to the binding of beta-2m and vice versa, and that regions of the molecule distal from the binding site influence the stability of peptide binding. RP PARKER, KC (reprint author), NIAID,BIOL RESOURCES BRANCH,BLDG 4,ROOM 413,BETHESDA,MD 20892, USA. OI Parker, Kenneth/0000-0002-6282-2478 NR 53 TC 117 Z9 119 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1992 VL 149 IS 6 BP 1896 EP 1904 PG 9 WC Immunology SC Immunology GA JN121 UT WOS:A1992JN12100011 PM 1517560 ER PT J AU KARP, SE HWU, P FARBER, A RESTIFO, NP KRIEGLER, M MULE, JJ ROSENBERG, SA AF KARP, SE HWU, P FARBER, A RESTIFO, NP KRIEGLER, M MULE, JJ ROSENBERG, SA TI INVIVO ACTIVITY OF TUMOR-NECROSIS-FACTOR (TNF) MUTANTS - SECRETORY BUT NOT MEMBRANE-BOUND TNF MEDIATES THE REGRESSION OF RETROVIRALLY TRANSDUCED MURINE TUMOR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN T-CELLS; FACTOR-ALPHA; FACTOR CACHECTIN; GENE-TRANSFER; LYMPHOCYTES; EXPRESSION; INHIBITION; TOXICITY; CACHEXIA; IMMUNITY AB We have previously demonstrated that murine tumor cells transduced with a retrovirus containing the cDNA encoding wild-type human TNF regress in vivo when injected into immunocompetent mice; this regression is T cell mediated. To determine whether membrane-associated or secreted TNF was responsible for tumor regression, we transduced a cloned murine fibrosarcoma 205 F4 with retroviruses encoding modified human TNF genes. The cloned tumor lines of one retroviral transduction expressed only membrane bound 26-kDa TNF. This TNF could not be cleaved or secreted, but was present on the cell surface. A second retrovirus caused the expression of only secretory 17-kDa TNF, as the transmembrane domain of the cDNA was deleted. The TNF produced by tumor cells transduced with either retroviral vector was functional in vitro as direct lysis of the TNF-sensitive target L929 by transduced tumor cells was demonstrated. The TNF present on 26-kDa expressing tumors was membrane bound as supernatants from cultured 17-kDa TNF expressing tumor cells but not 26-kDa TNF expressing tumors mediated the lysis of L929 cells. Both tumors were injected s.c. into syngeneic mice and tumor growth was measured serially. In repeated experiments, 26-kDa TNF expressing tumors grew progressively in all mice. In contrast, 17-kDa TNF expressing tumors grew for 10 days and then regressed with all animals free of tumor at 28 days. Tumor regression was abrogated by in vivo injection of an anti-TNF antibody. Similar results were obtained in a second tumor model, 203 E4. Thus regression of TNF transduced tumors in vivo requires secretion of TNF, as membrane-bound TNF is insufficient to elicit the host response. C1 NCI,SURG BRANCH,BLDG 10,ROOM 2B46,BETHESDA,MD 20892. CYTEL CORP,SAN DIEGO,CA 92121. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 21 TC 28 Z9 28 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1992 VL 149 IS 6 BP 2076 EP 2081 PG 6 WC Immunology SC Immunology GA JN121 UT WOS:A1992JN12100034 PM 1517571 ER PT J AU WEISS, WR BERZOFSKY, JA HOUGHTEN, RA SEDEGAH, M HOLLINDALE, M HOFFMAN, SL AF WEISS, WR BERZOFSKY, JA HOUGHTEN, RA SEDEGAH, M HOLLINDALE, M HOFFMAN, SL TI A T-CELL CLONE DIRECTED AT THE CIRCUMSPOROZOITE PROTEIN WHICH PROTECTS MICE AGAINST BOTH PLASMODIUM-YOELII AND PLASMODIUM-BERGHEI SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MALARIA SPOROZOITES; GAMMA-INTERFERON; FALCIPARUM; ANTIBODY; EPITOPES; DETERMINANT; INHIBITION; RECOGNIZE; MOLECULE; RECEPTOR AB Clone B is a cytotoxic T cell clone induced by immunization with Plasmodium yoelii sporozoites which recognizes an epitope on both the P. yoelii and Plasmodium berghei circumsporozoite proteins. It is CD8, uses the V-beta 8.1 TCR, and is K(d) restricted. When adoptively transferred, it protects mice against infection by both species of malaria sporozoites, and this protection is dependent on IFN-gamma. Clone B cells are more broadly reactive and protective than previously described murine T cell clones against malaria. Clone B may be an important model for immune protection against the spectrum of variant parasites in nature. C1 PAN AM HLTH ORG,WASHINGTON,DC 20037. BIOMED RES INST,ROCKVILLE,MD 20852. USN,MED RES INST,MALARIA PROGRAM,BETHESDA,MD 20899. NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20814. TORREY PINES INST MOLEC STUDIES,SAN DIEGO,CA 92121. NR 28 TC 97 Z9 97 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1992 VL 149 IS 6 BP 2103 EP 2109 PG 7 WC Immunology SC Immunology GA JN121 UT WOS:A1992JN12100038 PM 1517574 ER PT J AU RESZKA, KJ BILSKI, P CHIGNELL, CF HARTLEY, JA KHAN, N SOUHAMI, RL MENDONCA, AJ LOWN, JW AF RESZKA, KJ BILSKI, P CHIGNELL, CF HARTLEY, JA KHAN, N SOUHAMI, RL MENDONCA, AJ LOWN, JW TI PHOTOSENSITIZATION BY ANTICANCER AGENTS .11. MECHANISMS OF PHOTOSENSITIZATION OF HUMAN LEUKEMIC-CELLS BY DIAMINOANTHRAQUINONES - SINGLET OXYGEN AND RADICAL REACTIONS SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE AMINOANTHRAQUINONES; PHOTOSENSITIZATION; SINGLET OXYGEN; SPIN TRAPPING; SUPEROXIDE RADICAL; LEUKEMIC CELLS ID ANTITUMOR AGENTS; MOLECULAR-OXYGEN; VISIBLE-LIGHT; ROSE-BENGAL; NADH; DNA; ILLUMINATION; LUMINESCENCE; DERIVATIVES; OXIDATION AB The synthesis of several aminoanthraquinone derivatives (AAQs), designed to suppress the dark toxicity and to promote more efficient cancer cell photosensitization for potential use in photodynamic therapy (PDT), is described. The following AAQs were synthesized: 1-NH2-4,5-(MeO)2-AQ (1), 1,5-(NH2)2-4,8-(MeO)2-AQ (2), 1,8-(NH2)2-4,5-(MeO)2-AQ (3), and 1,5-(NHPhMe)2-4,8-(Meo)2-AQ (8). The agents exhibit strong absorption in the region 480-620 nm. Possible mechanisms of photosensitization were studied by measuring O-1(2) phosphorescence at 1270 nm, detecting superoxide radicals employing an electron paramagnetic resonance (EPR)-spin trapping technique, and measuring oxygen consumption during the photo-oxidation of a representative biological electron donor, NADH. Strong phosphorescence from O-1(2) was observed upon illumination of 2 and 3 in C6H6 (quantum yield of 0.25 and 0.5 respectively), and in EtOH (quantum yield of 0.23 and 0.34). The 1-amino-AQ (1) was the weakest O-1(2) sensitizer, with quantum yield of 0.13 in benzene. No phosphorescence was observed in EtOH. A superoxide radical was detected as a spin adduct of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) in irradiated benzene solutions of 1, 2 or 3 and DMPO. AAQs 2 and 3 sensitized photo-oxidation of NADH in H2O/EtOH mixture with the intermediacy of singlet oxygen as judged by the effect of sodium azide on the photostimulated oxygen consumption. Evolution of O2 upon addition of catalase to the illuminated solution confirmed the ultimate formation of hydrogen peroxide. These findings suggested that the (di)amino-dimethoxyanthraquinones might exert photosensitization via both Type I and Type II mechanisms. The AAQs were tested for their ability to photosensitize K562 human chronic myeloid leukemic cells in culture. Viability was measured using the 3,4,5-diethylthiazol-2,5-diphenyl tetrazolium blue assay, and DNA and possible membrane damage were assessed. The results from illuminating cells with light >475 nm show that for the 1,5-compounds, the presence of methoxy substituents at 4,8 positions reduces the dark toxicity from ID50 of 23 to 250 muM and for the 1,8-compounds correspondingly from ID50 of 53 to >300 muM. In the 1,5-series this decrease of the dark toxicity is accompanied by an increase in light-induced dose modification from 8.85 to 14.4.Differences exist in the mechanisms of cytotoxicity between the prototype phenolic AAQs and their methoxy counterparts. It appears that the cytotoxic action of the latter causes cell damage by the formation of a high proportion of alkali labile sites in addition to frank strand breaks. No evidence for membrane damage, as determined by transport of the model amino acid cycloleucine, could be observed even at supralethal doses. C1 UNIV ALBERTA, DEPT CHEM, EDMONTON T6G 2G2, ALBERTA, CANADA. NIEHS, MOLEC BIOPHYS LAB, RES TRIANGLE PK, NC 27709 USA. UCL, DEPT ONCOL, LONDON W1P 8BT, ENGLAND. UNIV LONDON MIDDLESEX HOSP, LONDON W1P 8BT, ENGLAND. NR 47 TC 27 Z9 27 U1 1 U2 4 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD SEP 15 PY 1992 VL 15 IS 4 BP 317 EP 335 DI 10.1016/1011-1344(92)85138-K PG 19 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JR299 UT WOS:A1992JR29900004 PM 1331388 ER PT J AU WANG, XJ GASPARD, P AF WANG, XJ GASPARD, P TI EPSILON ENTROPY FOR A TIME-SERIES OF THERMAL TURBULENCE SO PHYSICAL REVIEW A LA English DT Article ID STRANGE ATTRACTORS; CONVECTION; DIMENSION; EXPONENTS; SYSTEMS; CHAOS AB We consider a dynamic entropy of a Rayleigh-Benard flow which varies with the characteristic scales epsilon of the process. Such an epsilon entropy is used to distinguish and classify the different dynamic regimes recently observed in this system: oscillations, chaos, and soft, hard, and developed turbulences. Moreover, data analysis of an experimental time series reveals a scaling behavior of the epsilon entropy in a hard turbulent regime, demonstrating that this notion of entropy is suitable to describe dynamic processes with a hierarchy of characteristic instabilities. C1 UNIV CHICAGO,JAMES FRANCK INST,CHICAGO,IL 60637. NIDDKD,MATH RES BRANCH,BETHESDA,MD 20892. RP WANG, XJ (reprint author), UNIV CHICAGO,DEPT MATH,5734 S UNIV AVE,CHICAGO,IL 60637, USA. RI Wang, Xiao-Jing/D-2722-2009 NR 24 TC 11 Z9 11 U1 0 U2 0 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1050-2947 J9 PHYS REV A JI Phys. Rev. A PD SEP 15 PY 1992 VL 46 IS 6 BP R3000 EP R3003 PG 4 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA JQ375 UT WOS:A1992JQ37500008 ER PT J AU CLERICI, M ROILIDES, E VIA, CS PIZZO, PA SHEARER, GM AF CLERICI, M ROILIDES, E VIA, CS PIZZO, PA SHEARER, GM TI A FACTOR FROM CD8 CELLS OF HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS SUPPRESSES HLA SELF-RESTRICTED T-HELPER CELL RESPONSES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IMMUNOSUPPRESSION; ACQUIRED IMMUNODEFICIENCY SYNDROME; T-CELL IMMUNITY ID HIV; INTERLEUKIN-2; LYMPHOCYTES; EXPRESSION; HYBRIDOMAS; DEFICIENCY; ANTIBODIES; INHIBITION; PATHWAYS; INVITRO AB Defective in vitro T helper cell (T(h)) function can occur in asymptomatic human immunodeficiency virus (HIV)-seropositive (HIV+) individuals. A characteristic, early finding is the loss of an in vitro response to recall antigens, such as influenza A virus (FLU), despite an intact T(h) response to alloantigen (ALLO). To determine whether suppressor cells and/or inhibitory factors could contribute to this HIV-associated T(h) immunodeficiency, coculture studies were performed using peripheral blood leukocytes (PBLs) from monozygotic twins, one of whom was HIV-infected (HIV+) and one of whom was uninfected (HIV-seronegative, HIV-). In vitro T(h) function was measured as interleukin 2 production or proliferation to FLU and ALLO. Two pairs of twins were repetitively studied. A single HIV+ individual with multiple samples of cryopreserved PBLs over 6 years (including a HIV- specimen) was also studied. PBLs from the HIV+, but not from the HIV-, individuals demonstrated defective in vitro T(h) function in response to FLU but not to ALLO. PBLs from HIV+ individuals could induce a similar defect in the T(h) function of syngeneic or autologous HIV- PBLs. This suppression was generated by CD4-depleted, but not by CD8-depleted, PBLs. A suppressive factor from CD8+ cells of HIV+ donors was generated by 24-hr unstimulated cultures of HIV+ PBLs. This factor inhibited FLU but not ALLO responses of autologous, syngeneic, or allogeneic HIV- PBLs. This suppressive effect could not be explained by HIV infection or replication during the culture period. These results demonstrate that selective abrogation of T(h) function to recall antigens in HIV+ individuals is associated with an inhibitory factor produced by CD8+ T cells. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DIV RHEUMATOL & CLIN IMMUNOL,BALTIMORE,MD 21201. LOCH RAVEN VET ADM MED CTR,RES SERV,BALTIMORE,MD 21201. RP CLERICI, M (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 27 TC 26 Z9 26 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1992 VL 89 IS 18 BP 8424 EP 8428 DI 10.1073/pnas.89.18.8424 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300004 PM 1388269 ER PT J AU MIYATANI, S COPELAND, NG GILBERT, DJ JENKINS, NA TAKEICHI, M AF MIYATANI, S COPELAND, NG GILBERT, DJ JENKINS, NA TAKEICHI, M TI GENOMIC STRUCTURE AND CHROMOSOMAL MAPPING OF THE MOUSE N-CADHERIN GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GENE FAMILY; GENE DUPLICATION; CHROMOSOMAL LOCATION ID CELL-ADHESION MOLECULES; GLYCOPROTEIN-3 DESMOCOLLINS; DESMOSOMAL GLYCOPROTEIN-2; UVOMORULIN; FAMILY; CDNA; IDENTIFICATION; ORGANIZATION; CLONING; MEMBER AB N-cadherin is a member of the cadherin cell-cell adhesion receptor family that includes P-, E-, and R-cadherin and liver cell adhesion molecule (L-CAM). In this study, we determined the structure of the mouse N-cadherin gene by analyzing overlapping genomic clones obtained from a mouse genomic library. This gene consists of 16 exons that disperse over >200 kilobases of genomic DNA. This large size of the N-cadherin gene, compared with its cDNA (4.3 kilobases), is ascribed to the fact that the first and second introns are 34.2 kilobases and >100 kilobases long, respectively. When the N-cadherin gene was compared with that of L-CAM and P-cadherin, the exon-intron boundaries were found to be fully conserved between them, except that the P-cadherin first exon includes the first and second exons of the other two genes. Also, the second intron, which is equivalent to the first intron in P-cadherin, is exceptionally large and this structural feature is conserved in all of these genes. An interesting feature of the N-cadherin gene is that this gene has an extra 16th exon that is almost identical to the other exon, 100% in the coding region and 99% in the 3' untranslated region in the nucleotide level. We also determined the chromosomal localization of the N-cadherin gene by interspecific backcross analysis and found that this gene is localized in the proximal region of mouse chromosome 18. The E- and P-cadherin genes are tightly linked and located on chromosome 8 in this species. Thus, N-cadherin is unlinked to these other cadherin loci. C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,FREDERICK,MD 21701. RP MIYATANI, S (reprint author), KYOTO UNIV,FAC SCI,DEPT BIOPHYS,SAKYO KU,KYOTO 606,JAPAN. RI Takeichi, Masatoshi/G-5903-2012 OI Takeichi, Masatoshi/0000-0002-9931-3378 FU NCI NIH HHS [N01-CO-74101] NR 24 TC 58 Z9 59 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1992 VL 89 IS 18 BP 8443 EP 8447 DI 10.1073/pnas.89.18.8443 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300008 PM 1528849 ER PT J AU KRSMANOVIC, LZ STOJILKOVIC, SS MERELLI, F DUFOUR, SM VIRMANI, MA CATT, KJ AF KRSMANOVIC, LZ STOJILKOVIC, SS MERELLI, F DUFOUR, SM VIRMANI, MA CATT, KJ TI CALCIUM SIGNALING AND EPISODIC SECRETION OF GONADOTROPIN-RELEASING-HORMONE IN HYPOTHALAMIC NEURONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE VOLTAGE-SENSITIVE CALCIUM CHANNELS; CYTOPLASMIC CALCIUM; PULSATILE SECRETION ID RHESUS-MONKEY; MEDIOBASAL HYPOTHALAMUS; PULSE-GENERATOR; GNRH NEURONS; RAT HYPOTHALAMUS; LHRH; CHANNELS; INVITRO; INHIBITION; STEROIDS AB Gonadotropin-releasing hormone (GnRH) is released episodically into the pituitary portal vessels and from hypothalamic tissue of male and female rats in vitro. Perifused primary cultures of rat hypothalamic neurons, as well as the GT1-1 GnRH neuronal cell line, spontaneously exhibited episodic GnRH secretion of comparable frequency to that observed with perifused hypothalami. Such pulsatile GnRH release from GT1 cells indicates that GnRH neurons generate rhythmic secretory activity in the absence of input from other cell types. In primary hypothalamic cultures, the frequency of GnRH pulses increased with the duration of culture. The spontaneous pulsatility in GnRH release was abolished in Ca2+-deficient medium and was markedly attenuated in the presence of nifedipine, an antagonist of voltage-sensitive Ca2+ channels. The basal intracellular Ca2+ level of perifused GT1-1 cells cultured on coverslips was also dose-dependently reduced by nifedipine. Conversely, depolarization with high K+ increased intracellular Ca2+ and GnRH release in an extracellular Ca2+-dependent and nifedipine-sensitive manner. The dihydropyridine Ca2+ channel agonist Bay K 8644 increased basal and K+-induced elevations of intracellular Ca2+ concentration and GnRH secretion. These findings demonstrate that pulsatile neuropeptide secretion is an intrinsic property of GnRH neuronal networks and is dependent on voltage-sensitive Ca2+ influx for its maintenance. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, BLDG 10, ROOM B1-L400, BETHESDA, MD 20892 USA. NR 36 TC 171 Z9 173 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1992 VL 89 IS 18 BP 8462 EP 8466 DI 10.1073/pnas.89.18.8462 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300012 PM 1326758 ER PT J AU AMBUDKAR, SV LELONG, IH ZHANG, JP CARDARELLI, CO GOTTESMAN, MM PASTAN, I AF AMBUDKAR, SV LELONG, IH ZHANG, JP CARDARELLI, CO GOTTESMAN, MM PASTAN, I TI PARTIAL-PURIFICATION AND RECONSTITUTION OF THE HUMAN MULTIDRUG-RESISTANCE PUMP - CHARACTERIZATION OF THE DRUG-STIMULATABLE ATP HYDROLYSIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE OCTYL GLUCOSIDE; P-GLYCOPROTEIN; PROTEOLIPOSOME; VINBLASTINE; VERAPAMIL ID KB CARCINOMA-CELLS; P-GLYCOPROTEIN; MEMBRANE GLYCOPROTEIN; STREPTOCOCCUS-LACTIS; BACTERIAL TRANSPORT; DILUTE-SOLUTION; ANION-EXCHANGE; GENE-PRODUCT; MDR1 GENE; PROTEINS AB Multidrug-resistant human tumor cells over-express the MDR1 gene product P-glycoprotein, which is believed to function as an ATP-dependent efflux pump. In this study we demonstrate that the partially purified P-glycoprotein, when reconstituted in an artificial membrane, catalyzes drug-stimulated ATP hydrolysis. Plasma membrane proteins of a human multidrug-resistant cell line, KB-V1, were solubilized with 1.4% (wt/vol) octyl beta-D-glucopyranoside in the presence of 0.4% phospholipid and 20% (vol/vol) glycerol, and the crude detergent extract was chromatographed on DEAE-Sepharose CL-6B. The 0.1 M NaCl fraction, enriched in P-glycoprotein but devoid of Na,K-ATPase, was reconstituted by the detergent-dilution method. P-glycoprotein constituted 25-30% of the reconstituted protein in proteoliposomes. ATP hydrolysis by proteoliposomes was stimulated 3.5-fold by the addition of vinblastine but was unaffected by the hydrophobic antitumor agent camptothecin, which is not transported by P-glycoprotein. The stimulatory effect of vinblastine was observed only if the protein was reconstituted in proteoliposomes, suggesting that either the substrate binding site(s) was masked by detergent or that the conformation of the soluble P-glycoprotein might not be suitable for substrate-induced activation. Several other drugs that are known to be transported by P-glycoprotein enhanced the ATPase activity in a dose-dependent manner with relative potencies as follows: doxorubicin = vinblastine > daunomycin > actinomycin D > verapamil > colchicine. The basal and vinblastine-stimulated ATPase activities were inhibited by vanadate (50% inhibition observed at 7-10-mu-M) but were not affected by agents that inhibit other ATPases and phosphatases. These data indicate that the P-glycoprotein, similar to other ion-transporting ATPases, exhibits a high level of ATP hydrolysis (5-12-mu-mol per min per mg of protein). C1 NCI,CELL BIOL & MOLEC BIOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. RP AMBUDKAR, SV (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV NEPHROL,ROSS RES BLDG,ROOM 945,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. RI Ambudkar, Suresh/B-5964-2008 NR 36 TC 365 Z9 368 U1 2 U2 6 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1992 VL 89 IS 18 BP 8472 EP 8476 DI 10.1073/pnas.89.18.8472 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300014 PM 1356264 ER PT J AU EGAN, JJ GREENBERG, AS CHANG, MK WEK, SA MOOS, MC LONDOS, C AF EGAN, JJ GREENBERG, AS CHANG, MK WEK, SA MOOS, MC LONDOS, C TI MECHANISM OF HORMONE-STIMULATED LIPOLYSIS IN ADIPOCYTES - TRANSLOCATION OF HORMONE-SENSITIVE LIPASE TO THE LIPID STORAGE DROPLET SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DEPENDENT PROTEIN-KINASE; RAT ADIPOCYTES; SUBCELLULAR-DISTRIBUTION; PHOSPHORYLATION; INSULIN; CELLS AB Hormone-sensitive lipase activity (HSL), which is found in the supernatant of centrifuged homogenates of lipolytically quiet isolated rat adipocytes, was greatly reduced in or absent from the supernatant of lipolytically stimulated cells. The lipase was purified 100- to 250-fold from the supernatant of lipolytically quiet cells to 10-20% purity by a single passage over phenyl-Sepharose resin with high (>70%) activity yields. Western blotting of adipocyte homogenate fractions with polyclonal antiserum raised against HSL showed that the enzyme shifted quantitatively from the supernatant of control cells to the floating "fat cake" of lipolytically stimulated cells. A similar shift to the fat cake was observed when cells were disrupted by hypotonic lysis and centrifugation rather than by homogenization. We propose that upon lipolytic activation of adipocytes and phosphorylation of HSL by cAMP-dependent protein kinase, the critical event is not an increase in catalytic activity (i.e., turnover number) but a translocation of the lipase to its substrate at the surface of the lipid storage droplet. C1 NIDDKD,CELLULAR & DEV BIOL,MEMBRANE REGULAT SECT,BLDG 6,ROOM B1-15,BETHESDA,MD 20892. CTR BIOL EVALUAT & RES,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 25 TC 294 Z9 302 U1 0 U2 8 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1992 VL 89 IS 18 BP 8537 EP 8541 DI 10.1073/pnas.89.18.8537 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300027 PM 1528859 ER PT J AU FIORANI, M ROSA, MGP GATTASS, R ROCHAMIRANDA, CE AF FIORANI, M ROSA, MGP GATTASS, R ROCHAMIRANDA, CE TI DYNAMIC SURROUNDS OF RECEPTIVE-FIELDS IN PRIMATE STRIATE CORTEX - A PHYSIOLOGICAL-BASIS FOR PERCEPTUAL COMPLETION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MONKEY; VISUAL CORTEX; RECEPTIVE-FIELD STRUCTURE; OPTIC DISK; VISUAL PSYCHOPHYSICS ID MONKEY VISUAL-CORTEX; SOMATOSENSORY CORTEX; CEBUS MONKEY; RESPONSES; REORGANIZATION; NEURONS; V1; ORGANIZATION; WAVELENGTH; MECHANISMS AB Visual receptive fields (RFs) were mapped inside and outside the cortical representation of the optic disk in the striate cortex (area V1) of anesthetized and paralyzed Cebus monkeys. Unexpectedly, most cells were found to be binocularly driven, and the RFs mapped with contralateral-eye stimulation progressed in a topographically appropriate fashion as the optic disk sector was crossed. Activation of these neurons by the contralateral eye was shown to depend on stimulation of the parts of the retina around the optic disk. Outside the optic disk representation, a similar effect was demonstrated by obstructing the "classical" RF with masks 5-10 times larger in size. In all cases, visual stimuli presented around the mask could be used to accurately interpolate the position of the hidden RF. These properties reflect, at a cellular level, the process of "filling in" that allows for completion of the visual image across natural and artificially induced scotomas. C1 NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. RP FIORANI, M (reprint author), UNIV FED RIO DE JANEIRO, INST BIOFIS CARLOS CHAGAS FILHO, DEPT NEUROBIOL, BR-21941 RIO DE JANEIRO, BRAZIL. RI Rosa, Marcello/D-9278-2013 OI Rosa, Marcello/0000-0002-6620-6285 NR 31 TC 116 Z9 118 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1992 VL 89 IS 18 BP 8547 EP 8551 DI 10.1073/pnas.89.18.8547 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300029 PM 1528860 ER PT J AU BROWN, S AF BROWN, S TI ENGINEERED IRON OXIDE-ADHESION MUTANTS OF THE ESCHERICHIA-COLI PHAGE-LAMBDA RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LIGANDS; LIBRARY; BINDING; MALTOPORIN; MOLECULES; SEQUENCES; PROTEIN; GENE; DNA AB Escherichia coli able to specifically adhere to iron oxide and not adhere to other metal oxides were constructed by genetic engineering. Concatamers of random oligonucleotides were introduced into a portion of a plasmid-borne lamB gene encoding an external domain of the phage A receptor. Bacteria able to adhere to iron oxide were selected by serial enrichment from the population of plasmid transformants. The concatameric nature of the inserted DNA allows a genetic analysis analogous to exon shuffling. Results of this genetic analysis indicate that in some isolates, part of the binding site is encoded by flanking vector sequences. This strategy may prove generally useful for identifying protein sequences able to recognize specific surfaces. RP BROWN, S (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701, USA. OI Brown, Stanley/0000-0002-8453-8144 FU NCI NIH HHS [N01-CO-74101]; NCRR NIH HHS [S07-RR05761] NR 24 TC 192 Z9 195 U1 3 U2 20 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1992 VL 89 IS 18 BP 8651 EP 8655 DI 10.1073/pnas.89.18.8651 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300050 PM 1528875 ER PT J AU KALINEC, F HOLLEY, MC IWASA, KH LIM, DJ KACHAR, B AF KALINEC, F HOLLEY, MC IWASA, KH LIM, DJ KACHAR, B TI A MEMBRANE-BASED FORCE GENERATION MECHANISM IN AUDITORY SENSORY CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OUTER HAIR-CELLS; ELECTROKINETIC SHAPE CHANGES; GUINEA-PIG COCHLEA; SUBSURFACE CISTERNAE; SODIUM-CHANNELS; ORGAN; CORTI; CURRENTS; MOVEMENT; SPECTRIN AB Auditory outer hair cells can elongate and shorten at acoustic frequencies in response to changes of plasma membrane potential. We show that this fast bidirectional contractile activity consists of an electromechanical transduction process that occurs at the lateral plasma membrane and can be activated and analyzed independently in small membrane patches inside a patch electrode. Bidirectional forces are generated by increases and decreases in membrane area in response to hyperpolarization and depolarization, respectively. We suggest that the force generation mechanism is driven by voltage-dependent conformational changes within a dense array of large transmembrane proteins associated with the site of electromechanical transduction. C1 NIDOCD,CELLULAR BIOL LAB,BETHESDA,MD 20892. SCH MED SCI BRISTOL,DEPT PHYSIOL,BRISTOL BS8 1TD,ENGLAND. OI Iwasa, Kuni/0000-0002-9397-7704; Holley, Matthew/0000-0001-9547-1953 NR 33 TC 202 Z9 209 U1 0 U2 4 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1992 VL 89 IS 18 BP 8671 EP 8675 DI 10.1073/pnas.89.18.8671 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300054 PM 1528879 ER PT J AU OSWALD, IP WYNN, TA SHER, A JAMES, SL AF OSWALD, IP WYNN, TA SHER, A JAMES, SL TI INTERLEUKIN-10 INHIBITS MACROPHAGE MICROBICIDAL ACTIVITY BY BLOCKING THE ENDOGENOUS PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA REQUIRED AS A COSTIMULATORY FACTOR FOR INTERFERON-GAMMA-INDUCED ACTIVATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOKINE PRODUCTION; IFN-GAMMA; IL-10; CELL; EXPRESSION; MONOCYTES; MECHANISM; TOXICITY; SIGNALS AB Interleukin 10 (IL-10) inhibits interferon gamma-induced macrophage activation for cytotoxicity against larvae of the human parasite Schistosoma mansoni by suppressing production of the toxic effector molecule nitric oxide (NO). In this study, the mechanism of IL-10 action was identified as inhibition of endogenous tumor necrosis factor-alpha (TNF-alpha) production by interferon gamma-activated macrophages. TNF-alpha appears to serve as a cofactor for interferon gamma-mediated activation, since both schistosomulum killing and NO production were inhibited by anti-TNF-alpha antibody, whereas TNF-alpha alone was unable to stimulate these macrophage functions. IL-10 blocked TNF-alpha production by interferon gamma-treated macrophages at the levels of both protein and mRNA synthesis. Addition of exogenous TNF-alpha reversed IL-10-mediated suppression of macrophage cytotoxic activity as well as NO production. Likewise, addition of a macrophage-triggering agent (bacterial lipopolysaccharide or muramyl dipeptide), which induced the production of TNF-alpha, also reversed the suppressive effect of IL-10 on cytotoxic function. In contrast to IL-10, two other cytokines, IL-4 and transforming growth factor-beta, which also inhibit macrophage activation for schistosomulum killing and NO production, did not substantially suppress endogenous TNF-alpha production. These results, therefore, describe a separate pathway by which macrophage microbicidal function is inhibited by the down-regulatory cytokine IL-10. RP OSWALD, IP (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011; OSWALD, Isabelle/A-8497-2013; OI OSWALD, Isabelle/0000-0001-9918-277X NR 22 TC 315 Z9 318 U1 0 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1992 VL 89 IS 18 BP 8676 EP 8680 DI 10.1073/pnas.89.18.8676 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300055 PM 1528880 ER PT J AU WANK, SA PISEGNA, JR DEWEERTH, A AF WANK, SA PISEGNA, JR DEWEERTH, A TI BRAIN AND GASTROINTESTINAL CHOLECYSTOKININ RECEPTOR FAMILY - STRUCTURE AND FUNCTIONAL EXPRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GASTROINTESTINAL PEPTIDE RECEPTOR; NEUROPEPTIDE RECEPTOR; GUANINE NUCLEOTIDE-BINDING REGULATORY PROTEIN-COUPLED RECEPTOR ID PHARMACOLOGICAL CHARACTERIZATION; MOLECULAR CHARACTERIZATION; GASTRIN RECEPTORS; BOVINE RHODOPSIN; MESSENGER-RNAS; CDNA CLONING; GUINEA-PIG; RAT; BINDING; ANTAGONIST AB Cholecystokinin was one of the first gastrointestinal peptides discovered in the mammalian brain. In the central nervous system there is evidence for CCK(A) and CCK(B) receptor subtypes. The CCK(A) receptors occur in a few localized areas of the central and peripheral nervous systems where they modulate feeding and dopamine-induced behavior. CCK(B) receptors occur throughout the central nervous system where they modulate anxiety, analgesia, arousal, and neuroleptic activity. We have recently purified and cloned a CCK(A) receptor cDNA from rat pancreas that allowed isolation of an identical cDNA from rat brain by using the polymerase chain reaction. Using low-stringency hybridization screening of cDNA libraries from rat brain and AR42-J cells, which possess large numbers of CCK(B) receptors, we identified previously unreported cDNAs, the sequence of which were identical in both tissues. The cDNA sequence encodes a 452-amino acid protein that is 48% identical to the CCK(A) receptor and contains seven transmembrane domains characteristic of guanine nucleotide-binding regulatory protein-coupled receptors. COS-7 cells transfected with this cDNA expressed binding sites for agonists and antagonists characteristic of a CCK(B) receptor subtype. We conclude that this cDNA isolated from rat brain and AR42-J cells is a receptor of the CCK(B) subtype and that the respective cDNAs for both CCK(A) and CCK(B) are identical in the brain and gastrointestinal system. RP WANK, SA (reprint author), NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892, USA. NR 46 TC 436 Z9 441 U1 0 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1992 VL 89 IS 18 BP 8691 EP 8695 DI 10.1073/pnas.89.18.8691 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300058 PM 1528881 ER PT J AU KORALNIK, IJ GESSAIN, A KLOTMAN, ME LOMONICO, A BERNEMAN, ZN FRANCHINI, G AF KORALNIK, IJ GESSAIN, A KLOTMAN, ME LOMONICO, A BERNEMAN, ZN FRANCHINI, G TI PROTEIN ISOFORMS ENCODED BY THE PX REGION OF HUMAN T-CELL LEUKEMIA LYMPHOTROPIC VIRUS TYPE-I SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; BLOOD MONONUCLEAR-CELLS; HTLV-I; PERIPHERAL-BLOOD; MESSENGER-RNA; STRUCTURAL PROTEINS; EXPRESSION; SEQUENCE; FRESH; ANTIBODIES AB The pX region of the human T-cell leukemia/lymphotropic virus type I (HTLV-I) contains at least four open reading frames (orf I-orf IV). orf III and orf IV encode the regulatory HTLV-I proteins Rex and Tax, which together modulate viral expression, and the p21rex protein of unknown function. By using the reverse transcriptase and polymerase chain reaction techniques on the RNA of an HTLV-I-infected cell culture, we uncovered the existence of alternatively spliced mRNAs generated through the use of three splice acceptor sites. These mRNAs encoded protein isoforms derived from the HTLV-I orf I (p12I) and orf II (p13II and p30II). An additional acceptor splice site, used in the processing of the env and tax/rex mRNAs and a singly spliced mRNA for the p21rex protein, was also identified. All of these HTLV-I mRNAs were also detected in freshly isolated cells from HTLV-I-infected individuals. Thus HTLV-I, like the human immunodeficiency virus type 1, has developed fine posttranscriptional mechanisms to increase the complexity of its genome. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI klotman, mary/A-1921-2016 NR 37 TC 155 Z9 158 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1992 VL 89 IS 18 BP 8813 EP 8817 DI 10.1073/pnas.89.18.8813 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JN503 UT WOS:A1992JN50300083 PM 1528897 ER PT J AU NOGUCHI, K SENBA, E RUDA, MA AF NOGUCHI, K SENBA, E RUDA, MA TI INFLAMMATION - INDUCED INCREASE IN PREPROTACHYKININ MESSENGER-RNA IN A SUBPOPULATIONS OF LONG ASCENDING SPINAL TRACT CELLS IN THE RAT SO REGULATORY PEPTIDES LA English DT Meeting Abstract C1 WAKAYAMA MED COLL,DEPT ANAT & NEUROBIOL,WAKAYAMA 640,JAPAN. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD SEP 15 PY 1992 SU 1 BP S128 EP S128 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA JR149 UT WOS:A1992JR14900127 ER PT J AU NOGUCHI, K DELOEN, M SENBA, E RUDA, MA AF NOGUCHI, K DELOEN, M SENBA, E RUDA, MA TI AXOTOMY INDUCED CHANGE IN PREPROTACHYKININ MESSENGER-RNA EXPRESSION IN SUBPOPULATIONS OF DRG NEURON SO REGULATORY PEPTIDES LA English DT Meeting Abstract C1 WAKAYAMA MED COLL,DEPT ANAT & NEUROBIOL,WAKAYAMA 640,JAPAN. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD SEP 15 PY 1992 SU 1 BP S127 EP S127 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA JR149 UT WOS:A1992JR14900126 ER PT J AU KAFADAR, K STROUP, DF AF KAFADAR, K STROUP, DF TI ANALYSIS OF ABERRATIONS IN PUBLIC-HEALTH SURVEILLANCE DATA - ESTIMATING VARIANCES ON CORRELATED SAMPLES SO STATISTICS IN MEDICINE LA English DT Article ID BOOTSTRAP AB The detection of unusual patterns in health data presents an important challenge to health workers interested in early identification of epidemics or important risk factors. A useful procedure for detection of aberrations is the ratio of a current report to some historic baseline. This work addresses the problem of finding the variance of such a ratio when the surveillance reports are correlated. Results show that, when estimating this variance or the variance of the sample mean from a series of observations with an estimated correlation structure, bootstrap and jackknife estimates may be overly optimistic. The delta method or a classical method may be more useful when such model dependence is inappropriate. C1 CTR DIS CONTROL,EPIDEMIOL PROGRAM OFF,ATLANTA,GA 30333. RP KAFADAR, K (reprint author), NCI,BETHESDA,MD 20892, USA. NR 14 TC 8 Z9 8 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 15 PY 1992 VL 11 IS 12 BP 1551 EP 1568 DI 10.1002/sim.4780111203 PG 18 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA JX708 UT WOS:A1992JX70800002 PM 1332172 ER PT J AU KASPRZAK, KS NORTH, SL HERNANDEZ, L AF KASPRZAK, KS NORTH, SL HERNANDEZ, L TI REVERSAL BY NICKEL(II) OF INHIBITORY EFFECTS OF SOME SCAVENGERS OF ACTIVE OXYGEN SPECIES UPON HYDROXYLATION OF 2'-DEOXYGUANOSINE INVITRO SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE NICKEL; HISTIDINE; DEOXYGUANOSINE HYDROXYLATION; 8-HYDROXY-2'-DEOXYGUANOSINE ID DAMAGE; RADICALS; DNA AB Effects of ethanol (EtOH), mannitol (Man), L-histidine (His) and glutathione (GSH) on the oxidation of 2'-deoxyguanosine (dG) to its 8-hydroxy derivative (8-OH-dG) with H2O2 plus L-ascorbic acid (Ascb) in the absence and presence of Ni(II) were investigated in order to unveil the nature of active oxygen species involved in that oxidation. In the absence of Ni(II), production of 8-OH-dG was inhibited by His much greater than GSH greater-than-or-equal-to GSSG (oxidized glutathione) much greater than EtOH, but not by Man. The latter tended to enhance the production of 8-OH-dG. In the presence of Ni(II), the inhibition by His, GSH and GSSG, but not EtOH, was prevented. The results indicate involvement of a 'crypto-hydroxyl' radical as the dG oxidizing species in both the absence and presence of Ni(II). Also, the results provide evidence that Ni(II) complexes with His, GSH and GSSG may lack antioxidant capacity. Moreover, the Ni(II) complex with His was found capable of enhancing 8-OH-dG production by the Ascb + H2O2 system to a greater extent than Ni(II) alone. Likewise, although to a lesser extent, the formation of 8-OH-dG was enhanced by the combination of Ni(II) and Man which do not form complexes at pH 7.4. Since His is a major Ni(II) carrier in animal tissues, the dG oxidation enhancing capacity of the Ni(II) complex with His may contribute to the toxic and carcinogenic effects of Ni(II). C1 FREDERICK CANC RES & DEV CTR,ABL BIOL RESPONSE PROGRAM,MACRO MOLEC STRUCT LAB,FREDERICK,MD 21702. RP KASPRZAK, KS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,RM 205,FREDERICK,MD 21702, USA. NR 24 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD SEP 14 PY 1992 VL 84 IS 1 BP 11 EP 19 DI 10.1016/0009-2797(92)90117-4 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA JQ452 UT WOS:A1992JQ45200002 PM 1327552 ER PT J AU OMATA, Y FRIEDMAN, FK AF OMATA, Y FRIEDMAN, FK TI THE EFFECT OF DILAUROYL-L-3-PHOSPHATIDYLCHOLINE ON THE INTERACTION BETWEEN CYTOCHROME-P-450 1A1 AND BENZO[A]PYRENE SO FEBS LETTERS LA English DT Article DE CYTOCHROME-P-450; DILAUROYL-L-3-PHOSPHATIDYLCHOLINE; BENZO[A]PYRENE ID LIVER MICROSOMAL CYTOCHROME-P-450; MONOCLONAL-ANTIBODIES; FATTY-ACIDS; REDUCTASE; PURIFICATION; SUBSTRATE; BINDING; SYSTEM AB Fluorescence quenching of benzo[a]pyrene (BP) by cytochrome P-450 1A1 was used to probe the effect of the lipid, dilauroyl-L-3-phophatidylcholine, on this substrate-enzyme interaction. In the presence of lipid, a monoclonal antibody to this P-450 maximally inhibited BP binding at an antibody-to-P-450 ratio of 1:2, corresponding to an antibody crosslinked P-450 complex. The antibody did not inhibit BP binding in the absence of lipid. These results indicate that when P-450 is subjected to the orientational constraints imposed by antibody-mediated crosslinking, the lipid alters the conformation or quanternary structure of the P-450 oligomer in a manner which changes its affinity for BP. C1 NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892. RI Friedman, Fred/D-4208-2016 NR 21 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 14 PY 1992 VL 309 IS 3 BP 249 EP 252 DI 10.1016/0014-5793(92)80782-C PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA JM800 UT WOS:A1992JM80000006 PM 1516694 ER PT J AU CHOI, AMK JACOBY, DB AF CHOI, AMK JACOBY, DB TI INFLUENZA VIRUS-A INFECTION INDUCES INTERLEUKIN-8 GENE-EXPRESSION IN HUMAN AIRWAY EPITHELIAL-CELLS SO FEBS LETTERS LA English DT Article DE INTERLEUKIN-8; AIRWAY EPITHELIAL CELL; VIRUS; GENE EXPRESSION; INFLAMMATION; CYTOKINE ID NEUTROPHIL CHEMOTACTIC FACTOR; MESSENGER-RNA; GENERATION; CYTOKINE; ACID AB To determine the role of the airway epithelial cell in mediating virus-induced inflammation, we infected primary cultures of human airway epithelial cells with human influenza type A/Port Chalmers/72 (H3N2). After two days, the medium was collected for measurement of the chemotactic cytokine interleukin-8 by enzyme-linked immunosorbent assay. The RNA was extracted from the cells for analysis of interleukin-8 mRNA by Northern blot analysis. Interleukin-8 production was more than doubled by viral infection, while interleukin-8 mRNA was increased four-fold. Thus induction of interleukin-8 gene expression in virus-infected airway epithelium may be an important early step leading to virus-induced airway inflammation. C1 JOHNS HOPKINS UNIV,CTR ASTHMA & ALLERGY,DIV PULM & CRIT CARE MED,BALTIMORE,MD 21224. NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. FU NHLBI NIH HHS [HL47126]; NIA NIH HHS [AG00516] NR 18 TC 116 Z9 118 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 14 PY 1992 VL 309 IS 3 BP 327 EP 329 DI 10.1016/0014-5793(92)80799-M PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA JM800 UT WOS:A1992JM80000023 PM 1516705 ER PT J AU BLAHA, I TOZSER, J KIM, Y COPELAND, TD OROSZLAN, S AF BLAHA, I TOZSER, J KIM, Y COPELAND, TD OROSZLAN, S TI SOLID-PHASE SYNTHESIS OF THE PROTEINASE OF BOVINE LEUKEMIA-VIRUS - COMPARISON OF ITS SPECIFICITY TO THAT OF HIV-2 PROTEINASE SO FEBS LETTERS LA English DT Article DE SOLID PHASE PEPTIDE SYNTHESIS; BLV PROTEINASE; SUBSTRATE SPECIFICITY ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHEMICAL SYNTHESIS; POL POLYPROTEINS; ENZYMATIC-ACTIVITY; ESCHERICHIA-COLI; PROTEASE; GAG; SUBSTRATE; INHIBITOR; PEPTIDE AB The 126-residue proteinase (PR) of bovine leukemia virus (BLV) was synthesized by solid-phase peptide synthesis and its activity was shown using various oligopeptide substrates representing cleavage sites in BLV, human T-cell leukemia virus type 1 (HTLV-1), murine leukemia virus (MuLV) and human immunodeficiency virus type 1 (HIV-1). The specificity of the BLV PR was also compared to that of chemically synthesized human immunodeficiency virus type 2 (HIV-2) PR. Many of the peptides were cleaved at the expected site, however, 6 out of 15 were hydrolyzed only by one of the PRs. Furthermore, one BLV peptide was processed differently by the two enzymes. These results, together with the relative activities and the lack of inhibition of BLV PR by two HIV-1 PR inhibitors, suggest that the BLV PR specificity is substantially different from that of HIV PRs. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC VIROL & CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 FU NCI NIH HHS [N01-CO-74101] NR 42 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 14 PY 1992 VL 309 IS 3 BP 389 EP 393 DI 10.1016/0014-5793(92)80813-V PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA JM800 UT WOS:A1992JM80000037 PM 1325379 ER PT J AU IIJIMA, S GREIG, NH GAROFALO, P SPANGLER, EL HELLER, B BROSSI, A INGRAM, DK AF IIJIMA, S GREIG, NH GAROFALO, P SPANGLER, EL HELLER, B BROSSI, A INGRAM, DK TI THE LONG-ACTING CHOLINESTERASE INHIBITOR HEPTYL-PHYSOSTIGMINE ATTENUATES THE SCOPOLAMINE-INDUCED LEARNING IMPAIRMENT OF RATS IN A 14-UNIT T-MAZE SO NEUROSCIENCE LETTERS LA English DT Article DE ACETYLCHOLINE; MEMORY; AGING; ALZHEIMERS DISEASE ID MEMORY; PERFORMANCE; RODENTS; TERM AB Heptyl-physostigmine (heptyl-Phy), a new carbamate derivative of physostigmine (Phy), has been assessed for potential clinical value by evaluating its in vitro activity against human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE), its duration of in vivo activity against rat plasma AChE, and its effects on attenuating a scopolamine-induced impairment in learning performance of young rats in a 14-unit T-maze. Heptyl-Phy demonstrated potent cholinesterase inhibition, with activity similar to that of Phy against AChE, IC50 values 21.7 +/- 2.0 nM and 27.9 +/- 2.4 nM, respectively, and significantly greater than that of Phy against BChE, IC50 values 5.0 +/- 0.1 nM and 16.0 +/-2.9 nM, respectively. Heptyl-Phy achieved maximum AChE inhibition of 92.5% at 60 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, heptyl-Phy at 1.0, 1.5, 2.0 or 3.0 mg/kg, or vehicle was administered i.p. to 52 3-month-old male Fischer-344 rats 60 min prior to maze training. Thirty minutes prior to training, each animal received either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg). Only a 2.0 mg/kg dose of heptyl-Phy significantly reduced the number of errors in scopolamine-treated rats. The other doses did not improve any aspect of maze performance. Although the therapeutic window of heptyl-Phy did not appear wide enough for clinical use, the longer duration of action of heptyl-Phy would appear beneficial. C1 NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,MOLEC PHYSIOL & GENET SECT,4940 EASTERN AVE,BALTIMORE,MD 21224. NIA,NEUROSCI LAB,BETHESDA,MD 20205. NIDDKD,STRUCT BIOL LAB,NAT PROD SECT,BETHESDA,MD 20205. NR 15 TC 16 Z9 16 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 14 PY 1992 VL 144 IS 1-2 BP 79 EP 83 DI 10.1016/0304-3940(92)90720-R PG 5 WC Neurosciences SC Neurosciences & Neurology GA JQ144 UT WOS:A1992JQ14400019 PM 1436716 ER PT J AU KOVACS, JA AF KOVACS, JA TI EFFICACY OF ATOVAQUONE IN TREATMENT OF TOXOPLASMOSIS IN PATIENTS WITH AIDS SO LANCET LA English DT Note ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ENCEPHALITIS; THERAPY; COMBINATION; INVITRO; GONDII; 566C80 AB Atovaquone (formerly 566C80) is a hydroxynaphthoquinone with potent activity against Toxoplasma in vitro and in laboratory animals. Eight patients with AIDS and presumed or biopsy confirmed toxoplasmosis who were intolerant of or had not responded to standard therapies were treated with oral atovaquone 750 mg four times a day. Seven patients showed radiographic improvement; the other remained radiographically stable. Six patients died 6-60 weeks after enrolment with no clinical (six) or necropsy (three) evidence of recurrent toxoplasmosis; two patients relapsed at 1 0 and 32 weeks. Toxicity was mild: only one patient required temporary discontinuation of drug due to a rash. Atovaquone is a well-tolerated drug that appears to be an effective alternative for patients with toxoplasmosis who are intolerant of standard therapies. RP KOVACS, JA (reprint author), NCI,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,BETHESDA,MD 20892, USA. NR 10 TC 109 Z9 110 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD SEP 12 PY 1992 VL 340 IS 8820 BP 637 EP 638 DI 10.1016/0140-6736(92)92172-C PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JM851 UT WOS:A1992JM85100005 PM 1355212 ER PT J AU DAVIS, DL HOEL, DG AF DAVIS, DL HOEL, DG TI TOBACCO-ASSOCIATED DEATHS SO LANCET LA English DT Letter RP DAVIS, DL (reprint author), NIEHS,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709, USA. NR 7 TC 8 Z9 8 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD SEP 12 PY 1992 VL 340 IS 8820 BP 666 EP 666 DI 10.1016/0140-6736(92)92196-M PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JM851 UT WOS:A1992JM85100020 PM 1355221 ER PT J AU VILLALOBOSMOLINA, R JOSEPH, JA ROTH, GS AF VILLALOBOSMOLINA, R JOSEPH, JA ROTH, GS TI ALPHA-1-ADRENERGIC STIMULATION OF LOW KM GTPASE IN RAT STRIATA IS DIMINISHED WITH AGE SO BRAIN RESEARCH LA English DT Note DE ALPHA-1-ADRENOCEPTOR; LOW KM GTPASE; RAT STRIATUM; AGE; G-PROTEIN ID G-PROTEINS; REGIONS; BRAIN AB The effect of norepinephrine and epinephrine on the activity of low K(m) GTPase was studied in striata from young and old rats. Results showed that the amines stimulated the low K(m) GTPase activity of both young and old animals in a concentration-dependent manner. There was no differential effect of the amines as a function of age, but the stimulated low K(m) GTPase activity was significantly lower in the aged tissue. C1 NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. NR 6 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 11 PY 1992 VL 590 IS 1-2 BP 303 EP 304 DI 10.1016/0006-8993(92)91110-Z PG 2 WC Neurosciences SC Neurosciences & Neurology GA JP668 UT WOS:A1992JP66800037 PM 1330215 ER PT J AU CHMURNY, GN KOLECK, MP HILTON, BD AF CHMURNY, GN KOLECK, MP HILTON, BD TI BRYOSTATINS REVISITED - A NEW BRYOSTATIN-3 AND THE USE OF NMR TO DETERMINE STEREOCHEMISTRY IN THE C-20-C-23 AREA SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SPECTROSCOPY; AGENTS RP CHMURNY, GN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP CHEM SYNTH & ANAL LAB,POB B,FREDERICK,MD 21702, USA. NR 7 TC 19 Z9 19 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD SEP 11 PY 1992 VL 57 IS 19 BP 5260 EP 5264 DI 10.1021/jo00045a049 PG 5 WC Chemistry, Organic SC Chemistry GA JN950 UT WOS:A1992JN95000049 ER PT J AU KASHANCHI, F DUVALL, JF BRADY, JN AF KASHANCHI, F DUVALL, JF BRADY, JN TI ELECTROPORATION OF VIRAL TRANSACTIVATOR PROTEINS INTO LYMPHOCYTE SUSPENSION CELLS SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI, MOLEC VIROL LAB, BETHESDA, MD 20892 USA. NR 6 TC 43 Z9 43 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 11 PY 1992 VL 20 IS 17 BP 4673 EP 4674 DI 10.1093/nar/20.17.4673 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JP423 UT WOS:A1992JP42300048 PM 1408778 ER PT J AU KNIGHT, M MILLER, A RAGHAVAN, N RICHARDS, C LEWIS, F AF KNIGHT, M MILLER, A RAGHAVAN, N RICHARDS, C LEWIS, F TI IDENTIFICATION OF A REPETITIVE ELEMENT IN THE SNAIL BIOMPHALARIA-GLABRATA - RELATIONSHIP TO THE REVERSE TRANSCRIPTASE-ENCODING SEQUENCE IN LINE-1 TRANSPOSONS SO GENE LA English DT Article DE RECOMBINANT DNA; SNAIL GENOMIC DNA; BAMHI REPEAT; GENOMIC LIBRARY; BACTERIOPHAGE-LAMBDA DASH; PARASITE ID SCHISTOSOMA-MANSONI; DROSOPHILA-MELANOGASTER; DNA-SEQUENCES; GENES; RETROTRANSPOSONS; GENOME; VIRUS AB BamHI-digested Biomphalaria glabrata DNA contains a repetitive 2.0-kb fragment which is readily discernible by ethidium bromide staining. We present evidence that this repetitive element is related at both the nucleotide and amino acid levels to long interspersed nuclear element (LINE)-like transposons. Although comparable elements have been described in several invertebrates, this is the first report of a molluscan homologue. In common with LINE transposons, an open reading frame in the B. glabrata element shows significant homology to reverse transcriptase - a feature believed to allow the dissemination of these elements in the eukaryotic genome. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP KNIGHT, M (reprint author), BIOMED RES INST,12111 PARKLAWN DR,ROCKVILLE,MD 20852, USA. FU NIAID NIH HHS [AI-27777] NR 26 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 10 PY 1992 VL 118 IS 2 BP 181 EP 187 DI 10.1016/0378-1119(92)90187-T PG 7 WC Genetics & Heredity SC Genetics & Heredity GA JM798 UT WOS:A1992JM79800004 PM 1380940 ER PT J AU CADILLA, C ISHAM, KR LEE, KL CHANG, LY JOHNSON, AC KENNEY, FT AF CADILLA, C ISHAM, KR LEE, KL CHANG, LY JOHNSON, AC KENNEY, FT TI INSULIN INCREASES TRANSCRIPTION OF RAT GENE-33 THROUGH CIS-ACTING ELEMENTS IN 5'-FLANKING DNA SO GENE LA English DT Article DE STABLE TRANSFECTION; REPORTER GENE; HEPATOMA CELLS; NUCLEAR EXTRACTS; INVITRO TRANSCRIPTION ID MESSENGER RIBONUCLEIC-ACID; GROWTH-HORMONE GENE; PHOSPHOENOLPYRUVATE CARBOXYKINASE; CHLORAMPHENICOL ACETYLTRANSFERASE; HEPATOMA-CELLS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; ENHANCER ELEMENTS; MAMMALIAN-CELLS; TRANSGENIC MICE; CULTURED-CELLS AB Gene 33 is a multihormonally-regulated rat gene whose transcription is rapidly and markedly enhanced by insulin in liver and cultured hepatoma cells. To examine the mechanism by which insulin regulates transcription, we have constructed chimeric plasmids in which expression of the bacterial cat gene, encoding chloramphenicol acetyltransferase (CAT), is governed by gene 33 promoter elements and contiguous sequences in DNA flanking the transcription start point (tsp). When transfected into H4IIE hepatoma cells, these constructs gave rise to stably transformed cell lines producing the bacterial CAT enzyme. This expression was increased by insulin treatment in a fashion resembling the effect of this hormone on transcription of the native gene. In vitro transcription assays in nuclear extracts also revealed increased transcription of the chimeric plasmids when the extracts were prepared from insulin-treated rat hepatoma cells. The results demonstrate that induction by insulin is mediated by cis-acting nucleotide sequences located between bp -480 to +27 relative to the tsp. C1 OAK RIDGE NATL LAB,DIV BIOL,POB 2009,OAK RIDGE,TN 37831. UNIV TENNESSEE,OAK RIDGE GRAD SCH BIOMED SCI,OAK RIDGE,TN 37830. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [T32 CA 09336] NR 38 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 10 PY 1992 VL 118 IS 2 BP 223 EP 229 DI 10.1016/0378-1119(92)90192-R PG 7 WC Genetics & Heredity SC Genetics & Heredity GA JM798 UT WOS:A1992JM79800009 PM 1511896 ER PT J AU KANEDA, N OSHIMA, M CHUNG, SY GUROFF, G AF KANEDA, N OSHIMA, M CHUNG, SY GUROFF, G TI SEQUENCE OF A RAT TIS11 CDNA, AN IMMEDIATE EARLY GENE INDUCED BY GROWTH-FACTORS AND PHORBOL ESTERS SO GENE LA English DT Note DE RECOMBINANT DNA; TPA-INDUCIBLE SEQUENCE; PRIMARY RESPONSE GENE; NERVE GROWTH FACTOR; EPIDERMAL GROWTH FACTOR; FIBROBLAST GROWTH FACTOR; PC12 PHEOCHROMOCYTOMA CELLS; ZN2+-FINGER PROTEIN ID MESSENGER-RNA; PHEOCHROMOCYTOMA CELLS; NUCLEOTIDE-SEQUENCE; PC12 CELLS; C-FOS; PROTEIN; INDUCTION AB We report here the nucleotide sequence of a rat TIS11 cDNA, an immediate early gene, induced by nerve growth factor and epidermal growth factor, by 12-O-tetradecanoyl phorbol-13-acetate, and other stimuli in PC12 pheochromocytoma cells. The deduced protein consists of 320 amino acid residues with two tandem repeats of a putative Zn2+-finger motif. C1 NICHHD,GROWTH FACTORS SECT,BLDG 6,RM 130,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT BIOCHEM,BETHESDA,MD 20814. NR 15 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 10 PY 1992 VL 118 IS 2 BP 289 EP 291 DI 10.1016/0378-1119(92)90202-Z PG 3 WC Genetics & Heredity SC Genetics & Heredity GA JM798 UT WOS:A1992JM79800019 PM 1511903 ER PT J AU GAIL, MH MARK, SD AF GAIL, MH MARK, SD TI EARLY ZIDOVUDINE AND SURVIVAL IN HIV-INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP GAIL, MH (reprint author), NCI,ROCKVILLE,MD 20892, USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 10 PY 1992 VL 327 IS 11 BP 815 EP 815 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JL661 UT WOS:A1992JL66100027 PM 1472233 ER PT J AU GREENWALD, P WITKIN, KM MALONE, WF BYAR, DP FREEDMAN, LS STERN, HR AF GREENWALD, P WITKIN, KM MALONE, WF BYAR, DP FREEDMAN, LS STERN, HR TI THE STUDY OF MARKERS OF BIOLOGICAL EFFECT IN CANCER PREVENTION RESEARCH TRIALS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL WORKSHOP ON THE EPIDEMIOLOGY OF CERVICAL CANCER AND HUMAN PAPILLOMAVIRUS CY NOV 25-28, 1991 CL BRUSSELS, BELGIUM SP COMMISS EUROPEAN COMMUNITIES, EUROPE AGAINST CANC PROGRAM, MINIST PUBLIC HLTH & ENVIRONM BELGIUM, DANISH CANC REGISTRY, DANISH CANC SOC ID FAMILIAL ADENOMATOUS POLYPOSIS; EPITHELIAL-CELL PROLIFERATION; INTERMEDIATE END-POINTS; TUMOR-DEVELOPMENT; ORAL LEUKOPLAKIA; CHEMOPREVENTION; CARCINOGENESIS; COLON; RETINOBLASTOMA; BIOMARKERS AB Biological markers may provide a valuable tool for the development of cancer prevention agents, for monitoring patient compliance to a selected intervention, or for further defining the carcinogenic process. This discussion focuses on markers of biological effect and the rationale for their use in cancer prevention trials. Recent studies with biological markers are investigating their incorporation into phase-I, -II, and -III chemoprevention clinical trial designs. Their use in clinical studies is expected to increase the number of agents that may be evaluated and to provide valuable information on the biological effectiveness of agents, doses, and schedules. Markers may also provide information to help in selecting high-risk groups for prevention research, and to indicate the pathways inhibited and the stage of carcinogenesis affected. Such information may prove of crucial importance in strengthening the rationale for long-term trials and other ancillary research. Biomarker research for colon carcinogenesis is discussed, including examples of a number of recent trials that may influence future progress in this area of prevention research. A crucial step in this process is marker validation as an aspect of major prospective observational and intervention studies where cancer incidence is the endpoint. We cannot be fully confident of markers as intermediate endpoints until the evidence from clinical trials is sufficiently strong to support major public health initiatives for prevention. C1 WEINBERG CONSULTING GRP INC,WASHINGTON,DC 20007. PROSPECT ASSOCIATES,ROCKVILLE,MD 20852. RP GREENWALD, P (reprint author), NCI,DIV CANC PREVENT & CONTROL,OFF DIRECTOR,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 51 TC 14 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 9 PY 1992 VL 52 IS 2 BP 189 EP 196 DI 10.1002/ijc.2910520206 PG 8 WC Oncology SC Oncology GA JM713 UT WOS:A1992JM71300005 PM 1521908 ER PT J AU ALBINI, A MELCHIORI, A GAROFALO, A NOONAN, DM BASOLO, F TARABOLETTI, G CHADER, GJ GIAVAZZI, R AF ALBINI, A MELCHIORI, A GAROFALO, A NOONAN, DM BASOLO, F TARABOLETTI, G CHADER, GJ GIAVAZZI, R TI MATRIGEL PROMOTES RETINOBLASTOMA CELL-GROWTH INVITRO AND INVIVO SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL WORKSHOP ON THE EPIDEMIOLOGY OF CERVICAL CANCER AND HUMAN PAPILLOMAVIRUS CY NOV 25-28, 1991 CL BRUSSELS, BELGIUM SP COMMISS EUROPEAN COMMUNITIES, EUROPE AGAINST CANC PROGRAM, MINIST PUBLIC HLTH & ENVIRONM BELGIUM, DANISH CANC REGISTRY, DANISH CANC SOC ID BINDING PROTEIN IRBP; TUMOR-CELLS; NUDE-MOUSE; ESTABLISHED HUMAN; MESSENGER-RNA; LAMININ; DIFFERENTIATION; CANCER; LINES; GENE AB Cells derived from retinoblastomas grow slowly in vitro and only very rarely form tumors in nude mice. Matrigel, a mixture of components normally found in basement membranes, promotes the growth of Y-79 and WERI-RbI retinoblastoma (Rb) cells when added to suspension cultures of the 2 Rb cell lines. It also substantially increases cell adhesion in vitro. Y-79 cells, seeded into a Matrigel matrix, form round colonies over a 3-week period similar to those of control, weakly metastatic murine melanoma cells. In vivo, s.c. co-injection of Matrigel with either Y-79 or WERI-RbI cells into nude mice promotes retinoblastoma tumor formation. Transplantation of as few as 1,000 cells allows for xenografting under these conditions, while no tumors were observed in the absence of Matrigel, even at 10 x 10(6) cells/inoculum. The tumors produced have the expected morphology and express an mRNA for a highly specific retina/retinoblastoma marker protein, the interphotoreceptor retinoid-binding protein. Thus, the xenografts obtained maintain the original morphological and molecular characteristics of the injected cells and represent a useful model for in vivo studies of retinoblastoma growth and treatment. C1 UNIV PISA,IST ANAT PATOL,I-56100 PISA,ITALY. IST RIC FARMACOL MARIO NEGRI,I-24100 BERGAMO,ITALY. NEI,BETHESDA,MD 20892. RP ALBINI, A (reprint author), IST NAZL RIC CANC,VIALE BENEDETTO XV 10,I-16132 GENOA,ITALY. RI Noonan, Douglas/A-8620-2010 OI Noonan, Douglas/0000-0001-8058-0719 NR 38 TC 39 Z9 40 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 9 PY 1992 VL 52 IS 2 BP 234 EP 240 DI 10.1002/ijc.2910520214 PG 7 WC Oncology SC Oncology GA JM713 UT WOS:A1992JM71300013 PM 1521911 ER PT J AU LU, L ZHOU, Z WU, B XIAO, M SHEN, RN WILLIAMS, DE KIM, YJ KWON, BS RUSCETTI, S BROXMEYER, HE AF LU, L ZHOU, Z WU, B XIAO, M SHEN, RN WILLIAMS, DE KIM, YJ KWON, BS RUSCETTI, S BROXMEYER, HE TI INFLUENCE OF RECOMBINANT HUMAN INTERLEUKIN (IL)-7 ON DISEASE PROGRESSION IN MICE INFECTED WITH FRIEND-VIRUS COMPLEX SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL WORKSHOP ON THE EPIDEMIOLOGY OF CERVICAL CANCER AND HUMAN PAPILLOMAVIRUS CY NOV 25-28, 1991 CL BRUSSELS, BELGIUM SP COMMISS EUROPEAN COMMUNITIES, EUROPE AGAINST CANC PROGRAM, MINIST PUBLIC HLTH & ENVIRONM BELGIUM, DANISH CANC REGISTRY, DANISH CANC SOC ID STIMULATES TYROSINE PHOSPHORYLATION; CLONAL PROLIFERATION; MURINE INTERLEUKIN-7; GROWTH-FACTOR; CELLS; RECEPTOR; LEUKEMIA; IL-7; LACTOFERRIN; EXPRESSION AB Recombinant human (rhu) IL-7 was evaluated for its influence on disease progression in mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC). DBA/2 mice were injected i.v. with FVC, and then treated s.c. with rhuIL-7. IL-7 significantly prolonged survival time and decreased spleen focus-forming virus (SFFV) levels, expression of SFFV mRNA and SFFV protein production in FVC-infected mice. IL-7 did not appear to directly inactivate SFFV. Although both splenic weight and cellularity in FVC-infected mice treated with IL-7 were higher than those of normal mice, they were respectively 58% and 66% lower than those of the untreated FVC-infected mice. NK-cell activity was substantially lower in FVC-infected mice than in normal mice, while IL-7 restored NK-cell activity to normal levels. IL-6 and IFN-gamma levels were markedly reduced in FVC-infected mice compared to normal mice, but treatment of FVC-infected mice with IL-7 restored these cytokine levels. While the actual mechanisms of these effects are not yet known, the results suggest the potential therapeutic efficacy of IL-7 for certain hematopoietic and viral disorders, possibly mediated through an action on accessory cells and cytokine production. C1 INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT HEMATOL ONCOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT MICROBIOL IMMUNOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT RADIAT ONCOL,INDIANAPOLIS,IN 46202. IMMUNEX CORP,DEPT EXPTL HEMATOL,SEATTLE,WA. NCI,MOLEC ONCOL LAB,BETHESDA,MD 20892. RP LU, L (reprint author), INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,975 W WALNUT ST,1B 501,INDIANAPOLIS,IN 46202, USA. FU NCI NIH HHS [R37 CA-36464]; NHLBI NIH HHS [R01 HL46549, R01 HL49202] NR 22 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 9 PY 1992 VL 52 IS 2 BP 261 EP 265 DI 10.1002/ijc.2910520218 PG 5 WC Oncology SC Oncology GA JM713 UT WOS:A1992JM71300017 PM 1521912 ER PT J AU HEALY, B AF HEALY, B TI VACCINE DEVELOPMENT INITIATIVE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 9 PY 1992 VL 268 IS 10 BP 1248 EP 1248 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JL608 UT WOS:A1992JL60800007 ER PT J AU HEALY, B AF HEALY, B TI CONDOM INNOVATION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 9 PY 1992 VL 268 IS 10 BP 1248 EP 1248 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JL608 UT WOS:A1992JL60800006 ER PT J AU HEALY, B AF HEALY, B TI RESEARCH PROGRESS ON NEW AND BETTER METHODS FOR FAMILY-PLANNING SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 9 PY 1992 VL 268 IS 10 BP 1248 EP 1248 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JL608 UT WOS:A1992JL60800005 ER PT J AU PSATY, BM FURBERG, CD KULLER, LH BORHANI, NO RAUTAHARJU, PM OLEARY, DH BILD, DE ROBBINS, J FRIED, LP REID, C AF PSATY, BM FURBERG, CD KULLER, LH BORHANI, NO RAUTAHARJU, PM OLEARY, DH BILD, DE ROBBINS, J FRIED, LP REID, C TI ISOLATED SYSTOLIC HYPERTENSION AND SUBCLINICAL CARDIOVASCULAR-DISEASE IN THE ELDERLY - INITIAL FINDINGS FROM THE CARDIOVASCULAR HEALTH STUDY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID UNRECOGNIZED MYOCARDIAL-INFARCTION; CAROTID ATHEROSCLEROSIS; RISK-FACTORS; POPULATION; DETERMINANTS; HYPERTROPHY; PREVALENCE; MORTALITY; TRIAL AB Objective.-To assess the association between isolated systolic hypertension (ISH) and subclinical disease in adults aged 65 years and above. Design.-Medicare eligibility lists were used to obtain a representative sample of 5201 community-dwelling elderly persons for the Cardiovascular Health Study, a National Heart, Lung, and Blood Institute-sponsored cohort study of risk factors for coronary heart disease and stroke. In this cross-sectional analysis of baseline data, we excluded 3012 participants who were receiving antihypertensive medications, had clinical cardiovascular disease, or had a diastolic blood pressure of at least 90 mm Hg. Main Outcome Measures.-For electrocardiogram: myocardial infarction, left ventricular hypertrophy, and left ventricular mass as measures of myocardial damage and strain; for echocardiography: left ventricular mass, fractional shortening, and Doppler flow velocities as measures of cardiac systolic and diastolic function; and for carotid sonography: carotid arterial intima-media thickness as a measure of atherosclerosis. Results.-Among the 2189 men and women in this analysis, 195 (9%) had ISH (systolic blood pressure, greater-than-or-equal-to 160 mm Hg) and 596 (23%) had borderline ISH (systolic blood pressure, 140 to 159 mm Hg). Systolic blood pressure was associated with myocardial infarction by electrocardiogram (P=.02). Borderline and definite ISH were strongly associated with left ventricular mass (P<.001). While there was little association with cardiac systolic function, borderline and definite ISH were associated with cardiac diastolic function (P<.001). Isolated systolic hypertension was also strongly associated with increased intima-media thickness of the carotid artery (P<.001). Conclusions.-While cohort analyses of future repeated measures will provide a better assessment of risk, both borderline and definite ISH were strongly related to a variety of measures of subclinical disease in elderly men and women. C1 UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98105. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98105. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV PITTSBURGH,DEPT EPIDEMIOL,PITTSBURGH,PA 15260. CARDIOVASC HLTH STUDY COORDINATING CTR,SEATTLE,WA. UNIV ALBERTA,DEPT MED,EDMONTON T6G 2E1,ALBERTA,CANADA. GEISINGER MED CTR,DANVILLE,PA 17822. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892. UNIV CALIF DAVIS,DEPT MED,DAVIS,CA 95616. JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD 21218. UNIV CALIF IRVINE,DEPT MED,IRVINE,CA 92717. RP PSATY, BM (reprint author), UNIV WASHINGTON,COORDINATING CTR,DEPT MED,JD-30,1107 NE 45TH ST,SUITE 530,SEATTLE,WA 98105, USA. FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85080, N01-HC-85081] NR 32 TC 138 Z9 141 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 9 PY 1992 VL 268 IS 10 BP 1287 EP 1291 DI 10.1001/jama.268.10.1287 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JL608 UT WOS:A1992JL60800029 PM 1387172 ER PT J AU FERRIS, FL KASSOFF, A BUZNEY, SM MCMEEL, JW WEITER, JJ DOYLE, GJ IMMERMAN, RL FRIEDMAN, GR KLEIN, ML DREYER, R CHENOWETH, R HANDELMAN, I HOHL, R BIESBROECK, R SIPPERLEY, J GARCIA, CA BLOOME, MA RUIZ, RS RIEKHOF, FT BOHART, WA GOODART, RA CLARKE, DH ORTH, DH FLOOD, TP PACKO, KH MALHOTRA, J RAHMANI, A WINTER, EJ BHATIA, H MURPHY, RP FINE, SL ELMAN, MJ PROUT, TE PATZ, A RICE, TA NEWSOME, D AIELLO, LM RAND, LI SHAH, ST COOPPAN, R CAVALLERANO, J POOLE, R SILVER, P BRIONES, J WAFAI, MZ ASMAL, AC FRANKLIN, RM AREND, L BERGSMA, D TURKISH, L BEER, P CARROLL, D THOMAS, E BURTON, TC ABRAMS, GW KIM, HJ WILLIAMS, GA TOPPING, TM REESER, FH AABERG, TM BRINTON, GS KINGHAM, JK MEREDITH, TA MARGHERIO, RR MURPHY, PL COX, MS TRESE, M WINOKUR, S AI, E SORENSON, R ARSHAM, G CAVENDER, J KOPELOW, SM SHABO, AL BRIONES, JC HORNICHTER, RD BLAIR, NP GOLDBERG, MF LINDBERG, CR ROSS, NL HAUSER, LE CUNHAVAZ, J ERNEST, JT LIANG, JC COHEN, SB VYGANTAS, C WILLIAMS, G FLYNN, HW BLANKENSHIP, GW KNOBLOCH, WH RAMSAY, RC CANTRILL, HL GOETZ, FC HOOGWERF, B BERROCAL, J PEREZ, R UMPIERRE, AR KINYOUN, JL KALINA, RE WELLS, CG GUZAK, SV PALMER, J MYERS, FL BRESNICK, GH CHANDRA, SR DAVIS, MD KLEIN, R STEVENS, TS WALLOW, IH DIXON, R EHRLICH, E EWART, R FRANK, RN LUCAS, S WHITEHOUSE, F WEISS, H BALLEN, AE TESKE, M WARTH, M BENSON, WE TASMAN, WS BROWN, GC MCNAMARA, JA LITTLE, HL JACK, RL BASSO, L MILLER, DT GUNTER, E BAYSE, DD HANNON, WH MYRICK, JE KNATTERUD, GL FISHER, MR PRIOR, MJ BARTON, F KUFERA, J MILLER, TW HOOPER, JK CROW, RS BAKER, RR PRINEAS, R DAVIS, MD HUBBARD, LD MAGLI, YL SEGAL, P MOWERY, RL CHEW, EY SEIGEL, DG CASSEL, G AF FERRIS, FL KASSOFF, A BUZNEY, SM MCMEEL, JW WEITER, JJ DOYLE, GJ IMMERMAN, RL FRIEDMAN, GR KLEIN, ML DREYER, R CHENOWETH, R HANDELMAN, I HOHL, R BIESBROECK, R SIPPERLEY, J GARCIA, CA BLOOME, MA RUIZ, RS RIEKHOF, FT BOHART, WA GOODART, RA CLARKE, DH ORTH, DH FLOOD, TP PACKO, KH MALHOTRA, J RAHMANI, A WINTER, EJ BHATIA, H MURPHY, RP FINE, SL ELMAN, MJ PROUT, TE PATZ, A RICE, TA NEWSOME, D AIELLO, LM RAND, LI SHAH, ST COOPPAN, R CAVALLERANO, J POOLE, R SILVER, P BRIONES, J WAFAI, MZ ASMAL, AC FRANKLIN, RM AREND, L BERGSMA, D TURKISH, L BEER, P CARROLL, D THOMAS, E BURTON, TC ABRAMS, GW KIM, HJ WILLIAMS, GA TOPPING, TM REESER, FH AABERG, TM BRINTON, GS KINGHAM, JK MEREDITH, TA MARGHERIO, RR MURPHY, PL COX, MS TRESE, M WINOKUR, S AI, E SORENSON, R ARSHAM, G CAVENDER, J KOPELOW, SM SHABO, AL BRIONES, JC HORNICHTER, RD BLAIR, NP GOLDBERG, MF LINDBERG, CR ROSS, NL HAUSER, LE CUNHAVAZ, J ERNEST, JT LIANG, JC COHEN, SB VYGANTAS, C WILLIAMS, G FLYNN, HW BLANKENSHIP, GW KNOBLOCH, WH RAMSAY, RC CANTRILL, HL GOETZ, FC HOOGWERF, B BERROCAL, J PEREZ, R UMPIERRE, AR KINYOUN, JL KALINA, RE WELLS, CG GUZAK, SV PALMER, J MYERS, FL BRESNICK, GH CHANDRA, SR DAVIS, MD KLEIN, R STEVENS, TS WALLOW, IH DIXON, R EHRLICH, E EWART, R FRANK, RN LUCAS, S WHITEHOUSE, F WEISS, H BALLEN, AE TESKE, M WARTH, M BENSON, WE TASMAN, WS BROWN, GC MCNAMARA, JA LITTLE, HL JACK, RL BASSO, L MILLER, DT GUNTER, E BAYSE, DD HANNON, WH MYRICK, JE KNATTERUD, GL FISHER, MR PRIOR, MJ BARTON, F KUFERA, J MILLER, TW HOOPER, JK CROW, RS BAKER, RR PRINEAS, R DAVIS, MD HUBBARD, LD MAGLI, YL SEGAL, P MOWERY, RL CHEW, EY SEIGEL, DG CASSEL, G TI ASPIRIN EFFECTS ON MORTALITY AND MORBIDITY IN PATIENTS WITH DIABETES-MELLITUS - EARLY TREATMENT DIABETIC-RETINOPATHY STUDY REPORT-14 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID VASCULAR-DISEASE; FOLLOW-UP; PLATELETS; AGGREGATION AB Objectives.-This report presents information on the effects of aspirin on mortality, the occurrence of cardiovascular events, and the incidence of kidney disease in the patients enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS). Study Design.-This multicenter, randomized clinical trial of aspirin vs placebo was sponsored by the National Eye Institute. Patients.-Patients (N=3711) were enrolled in 22 clinical centers between April 1980 and July 1985. Men and women between the ages of 18 and 70 years with a clinical diagnosis of diabetes mellitus were eligible. Approximately 30% of all patients were considered to have type I diabetes mellitus, 31 % type II, and in 39% type I or II could not be determined definitely. Intervention.-Patients were randomly assigned to aspirin or placebo (two 325-mg tablets once per day). Main Outcome Measures.-Mortality from all causes was specified as the primary outcome measure for assessing the systemic effects of aspirin. Other outcome variables included cause-specific mortality and cardiovascular events. Results.-The estimate of relative risk for total mortality for aspirin-treated patients compared with placebo-treated patients for the entire study period was 0.91 (99% confidence interval, 0.75 to 1.11). Larger differences were noted for the occurrence of fatal and nonfatal myocardial infarction; the estimate of relative risk was 0.83 for the entire follow-up period (99% confidence interval, 0.66 to 1.04). Conclusions.-The effects of aspirin on any of the cardiovascular events considered in the ETDRS were not substantially different from the effects observed in other studies that included mainly nondiabetic persons. Furthermore, there was no evidence of harmful effects of aspirin. Aspirin has been recommended previously for persons at risk for cardiovascular disease. The ETDRS results support application of this recommendation to those persons with diabetes at increased risk of cardiovascular disease. C1 UNION UNIV, ALBANY, NY 12208 USA. RETINA FDN RETINA ASSOCIATES, EYE RES INST, BOSTON, MA USA. GOOD SAMARITAN HOSP, PORTLAND, OR 97210 USA. UNIV TEXAS, HERMANN EYE CTR, HOUSTON, TX 77025 USA. HOLY CROSS HOSP, SALT LAKE CITY, UT USA. INGALLS MEM HOSP, HARVEY, IL USA. JOHNS HOPKINS UNIV HOSP, WILMER INST, BALTIMORE, MD 21205 USA. JOSLIN DIABET CTR, BEETHAM EYE INST, BOSTON, MA USA. LOUISIANA STATE UNIV, CTR EYE, NEW ORLEANS, LA USA. MED COLL WISCONSIN, MILWAUKEE, WI 53226 USA. MICHIGAN STATE UNIV, ASSOCIATED RETINA CONSULTANTS, E LANSING, MI 48824 USA. PACIFIC PRESBYTERIAN MED CTR, SAN FRANCISCO, CA USA. UNIV CALIF LOS ANGELES, CTR HLTH SCI, JULES STEIN EYE INST, LOS ANGELES, CA 90024 USA. UNIV ILLINOIS, CHICAGO, IL 60680 USA. UNIV MIAMI, SCH MED, BASCOM PALMER EYE INST, MIAMI, FL 33152 USA. UNIV MINNESOTA, CTR ECG CODING, MINNEAPOLIS, MN 55455 USA. UNIV PUERTO RICO, RIO PIEDRAS, PR 00931 USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. UNIV WISCONSIN, CTR FUNDUS PHOTOG READING, MADISON, WI 53706 USA. WAYNE STATE UNIV, KRESGE EYE INST, DETROIT, MI 48202 USA. WILLS EYE HOSP & RES INST, PHILADELPHIA, PA 19107 USA. ZWENG MEM RETINAL RES FDN, MENLO PK, CA USA. CTR DIS CONTROL, CENT LAB, ATLANTA, GA 30333 USA. MARYLAND MED RES INST, COORDINATING CTR, BALTIMORE, MD USA. US PHS, CTR DRUG DISTRIBUT, PERRY POINT, MD USA. RP FERRIS, FL (reprint author), NEI, BIOMETRY & EPIDEMIOL PROGRAM, ROOM 6A-24, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 35 TC 267 Z9 275 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 9 PY 1992 VL 268 IS 10 BP 1292 EP 1300 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA JL608 UT WOS:A1992JL60800030 ER PT J AU COOPER, JR CZECHOWICZ, DJ PETERSEN, RC MOLINARI, SP AF COOPER, JR CZECHOWICZ, DJ PETERSEN, RC MOLINARI, SP TI PRESCRIPTION DRUG DIVERSION CONTROL AND MEDICAL-PRACTICE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CATCHMENT-AREA SITES; UNITED-STATES; CHRONIC PAIN; BENZODIAZEPINES; ABUSE; PREVALENCE; DEPRESSION; DISORDER; PROGRAM; QUALITY AB Concern about the role of prescription drug diversion in drug abuse has led to demands for more stringent regulation and for better ways to detect prescription drug diversion. Advances in technology now allow point-of-sale computer systems to report prescriptions filled by pharmacies to state agencies rapidly and possibly more economically. However, the advantages of more comprehensive control systems must be balanced against their possible effects on medical practice and patient care. Our limited knowledge about prescription drug diversion and the impact of diversion control systems on medical practice is summarized. Needed research is outlined together with the components of a diversion control program that balances reducing drug diversion with minimizing adverse effects on medical practice and patient care. We stress the need for broadly defined practice parameters and peer review by medical experts thoroughly familiar with the complexities of medical practice. C1 NIDA,ROCKVILLE,MD. NR 93 TC 25 Z9 25 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 9 PY 1992 VL 268 IS 10 BP 1306 EP 1310 DI 10.1001/jama.268.10.1306 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JL608 UT WOS:A1992JL60800032 PM 1507377 ER PT J AU HALL, WH GOLDSMITH, LA ASKIN, FB CHANG, AE COHEN, C DUTCHER, JP GILGOR, RS GREEN, S HARRIS, EL HAVAS, S ROBINSON, JK SWANSON, NA TEMPERO, MA AF HALL, WH GOLDSMITH, LA ASKIN, FB CHANG, AE COHEN, C DUTCHER, JP GILGOR, RS GREEN, S HARRIS, EL HAVAS, S ROBINSON, JK SWANSON, NA TEMPERO, MA TI DIAGNOSIS AND TREATMENT OF EARLY MELANOMA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 UNIV ROCHESTER,SCH MED,DEPT DERMATOL,ROCHESTER,NY 14627. JOHNS HOPKINS UNIV HOSP,SURG PATHOL,BALTIMORE,MD 21205. UNIV MICHIGAN,DIV SURG ONCOL,ANN ARBOR,MI 48109. EMORY UNIV,SCH MED,DEPT ANAT PATHOL,ATLANTA,GA 30322. MONTEFIORE MED CTR,ALBERT EINSTEIN CANC CTR,DEPT ONCOL,BRONX,NY 10467. UNIV N CAROLINA,DERMATOL,CHAPEL HILL,NC 27514. DUKE UNIV,DERMATOL,DURHAM,NC 27706. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. UNIV WASHINGTON,SEATTLE,WA 98195. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. NORTHWESTERN UNIV,SCH MED,DEPT DERMATOL,CHICAGO,IL 60611. OREGON HLTH SCI UNIV,DERMATOL SURG & ONCOL SECT,PORTLAND,OR 97201. UNIV NEBRASKA,MED CTR,DEPT INTERNAL MED,ONCOL HEMATOL SECT,OMAHA,NE 68105. RP HALL, WH (reprint author), NIH,OFF MED APPLICAT RES,FED BLDG,ROOM 618,BETHESDA,MD 20892, USA. NR 0 TC 247 Z9 249 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 9 PY 1992 VL 268 IS 10 BP 1314 EP 1319 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA JL608 UT WOS:A1992JL60800034 ER PT J AU PARRIS, KD HOOVER, DJ DAMON, DB DAVIES, DR AF PARRIS, KD HOOVER, DJ DAMON, DB DAVIES, DR TI SYNTHESIS AND CRYSTALLOGRAPHIC ANALYSIS OF 2 RHIZOPUSPEPSIN INHIBITOR COMPLEXES SO BIOCHEMISTRY LA English DT Article ID X-RAY ANALYSES; PORCINE PANCREATIC ELASTASE; LEAST-SQUARES REFINEMENT; ASPARTIC PROTEINASE; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURE; RENIN INHIBITORS; 1.8-A RESOLUTION; FLUORO KETONE; PEPSIN AB The crystal structures of rhizopuspepsin complexed with two oligopeptide inhibitors have been determined. CP-69,799, an azahomostatine dipeptide isostere, had previously been associated with a displacement of the C-terminal subdomain of endothiapepsin [Sali, A., Veerapandian, B., Cooper, J. B., Foundling, S. I., Hoover, D. J., & Blundell, T. L. (1989) EMBO J. 8, 2179-21881. Here, we report the measurement of two data sets, one from crystals soaked in the inhibitor and the other from protein crystallized in the presence of excess inhibitor. In neither case is there any significant movement of the C-terminal subdomain of the rhizopuspepsin. The data suggest that the energy associated with any conformational change is small and is overcome by the crystal packing forces. The second inhibitor, a hydrated difluorostatone, was examined in a search for transition-state analogs that could cast further light on the mechanism of action [Suguna, K., Padlan, E. A., Smith, C. W., Carlson, W. D., & Davies, D. R. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 7009-7013]. The gem-diol provides a set of contact distances with the enzyme that mimic the interactions with the tetrahedral intermediate of the substrate during catalysis. These data provide support for the suggestion that the polarization of the keto group of the peptide substrate is enhanced by a hydrogen bond from the OD1 of Asp 35 (Suguna et al., 1987). C1 NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. PFIZER INC,DIV CENT RES,DEPT MED CHEM,GROTON,CT 06340. NR 67 TC 31 Z9 31 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 8 PY 1992 VL 31 IS 35 BP 8125 EP 8141 DI 10.1021/bi00150a004 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM572 UT WOS:A1992JM57200004 PM 1525154 ER PT J AU GRZESIEK, S DOBELI, H GENTZ, R GAROTTA, G LABHARDT, AM BAX, A AF GRZESIEK, S DOBELI, H GENTZ, R GAROTTA, G LABHARDT, AM BAX, A TI H-1, C-13, AND N-15 NMR BACKBONE ASSIGNMENTS AND SECONDARY STRUCTURE OF HUMAN INTERFERON-GAMMA SO BIOCHEMISTRY LA English DT Article ID TRIPLE-RESONANCE NMR; ISOTOPICALLY ENRICHED PROTEINS; HUMAN IMMUNE INTERFERON; LARGER PROTEINS; IFN-GAMMA; SEQUENTIAL ASSIGNMENT; BIOLOGICAL-ACTIVITY; HETERONUCLEAR NMR; CARBOXYL TERMINUS; CHEMICAL-SHIFTS AB H-1, C-13, and N-15 NMR assignments of the protein backbone of human interferon-gamma, a homodimer of 31.4 kDa, have been made using the recently introduced three-dimensional (3D) triple-resonance NMR techniques. It is shown that, despite the approximately 40-50-Hz C-13(alpha) and H-1(alpha) line widths of this high molecular weight dimer and the extensive overlap in the H-1(alpha) and C-13(alpha) spectral regions, unique sequential assignments can be made on the basis of combined use of the 3D HNCO, HNCA, HN(CO)CA, and HCACO constant-time experiments, the N-15-separated 3D NOESY-HMQC, and the 3D HOHAHA-HMQC experiments. Analysis of the N-15-separated 3D NOESY-HMQC and C-13/N-15-separated four-dimensional (4D) NOESY-HMQC spectra together with the secondary C(alpha) and C(beta) chemical shifts yielded extensive secondary structure information. The NMR-derived secondary structure essentially confirms results of a recently published low-resolution crystal structure [Ealick et al. (1991) Science 252, 698-7021, i.e., six helices in the monomer which are mostly alpha-helical in nature, no beta-sheets, a long flexible loop between helices A and B, and a very hydrophobic helix C. The functionally important carboxy terminus, which was not observed in the X-ray study, does not adopt a rigid conformation in solution. A high degree of internal mobility, starting at Pro-123, gives rise to significantly narrower resonance line widths for these carboxy-terminal residues compared to the rest of the protein. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. F HOFFMANN LA ROCHE & CO LTD,CH-4002 BASEL,SWITZERLAND. NR 61 TC 135 Z9 136 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 8 PY 1992 VL 31 IS 35 BP 8180 EP 8190 DI 10.1021/bi00150a009 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM572 UT WOS:A1992JM57200009 PM 1525157 ER PT J AU WOLFF, NA PHILPOT, RM MILLER, DS PRITCHARD, JB AF WOLFF, NA PHILPOT, RM MILLER, DS PRITCHARD, JB TI FUNCTIONAL EXPRESSION OF RENAL ORGANIC ANION TRANSPORT IN XENOPUS-LAEVIS OOCYTES SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE ORGANIC ANION TRANSPORT; SECRETION; P-AMINOHIPPURATE; DICARBOXYLIC ACIDS; KIDNEY; EXPRESSION IN XENOPUS-OOCYTES ID BASOLATERAL MEMBRANE-VESICLES; NA+/GLUCOSE CO-TRANSPORTER; BRUSH-BORDER MEMBRANES; PARA-AMINOHIPPURATE; MESSENGER-RNA; CDNA CLONING; P-AMINOHIPPURATE; PROXIMAL TUBULE; KIDNEY; EXCHANGE AB Secretion of organic anions by the kidney plays a critical role in the elimination of toxic agents from the body. Recent findings in isolated membranes and intact tissue have demonstrated the participation of multiple transport proteins in this process. As a first step toward molecular characterization of these proteins through expression cloning, the studies reported below demonstrate functional expression of both fumarate- and lithium-sensitive glutarate and probenecid-sensitive p-aminohippurate transport in Xenopus oocytes injected with rat kidney poly(A)+ RNA. Maximal increase in substrate uptake over buffer-injected controls was reached by 5 days after mRNA injection. Expression of size-fractionated mRNA indicated that the active species with respect to both transport activities were in the range of 1.8 to 3.5 kb. RP WOLFF, NA (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,POB 12233,MD 741,RES TRIANGLE PK,NC 27709, USA. NR 31 TC 12 Z9 12 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP 8 PY 1992 VL 114 IS 1-2 BP 35 EP 41 PG 7 WC Cell Biology SC Cell Biology GA JQ517 UT WOS:A1992JQ51700007 PM 1281263 ER PT J AU AMBUDKAR, IS LOCKWICH, T HIRAMATSU, Y BAUM, BJ AF AMBUDKAR, IS LOCKWICH, T HIRAMATSU, Y BAUM, BJ TI CALCIUM ENTRY IN RAT PAROTID ACINAR-CELLS SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE CA2+ INFLUX; CA2+ MOBILIZATION; NEUROTRANSMITTERS; PAROTID GLAND; EXOCRINE CELLS ID CYTOSOLIC FREE CALCIUM; INOSITOL PHOSPHATES; CA-2+ ENTRY; INFLUX; CHANNELS; POOL; ACTIVATION; RECEPTORS; MEMBRANE; RELEASE RP AMBUDKAR, IS (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892, USA. NR 30 TC 12 Z9 12 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP 8 PY 1992 VL 114 IS 1-2 BP 73 EP 77 PG 5 WC Cell Biology SC Cell Biology GA JQ517 UT WOS:A1992JQ51700012 PM 1461260 ER PT J AU FREUDENRICH, CC MURPHY, E LIU, S LIEBERMAN, M AF FREUDENRICH, CC MURPHY, E LIU, S LIEBERMAN, M TI MAGNESIUM HOMEOSTASIS IN CARDIAC-CELLS SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE MAGNESIUM; CALCIUM; HYDROGEN ION; FLUORESCENT DYES; HEART CELLS ID CHICK HEART-CELLS; CYTOSOLIC FREE MAGNESIUM; INTRACELLULAR MAGNESIUM; TRANSPORT; EXCHANGE; PH AB Several aspects of Mg2+ homeostasis were investigated in cultured chicken heart cells using the fluorescent Mg2+ indicator, FURAPTRA. The concentration of cytosolic Mg2+ ([Mg2+]i) is 0.48 +/- 0.03 mM (n = 31). To test whether a putative Na/Mg exchange mechanism controls [Mg2+]i below electrochemical equilibrium, we manipulated the Na+ gradient and assessed the effects on [Mg2+]i. When extracellular Na+ was removed, [Mg2+]i increased; this increase was not altered in Mg-free solutions, but was attenuated in Ca-free solutions. A similar increase in [Mg2+]i, which was dependent upon extracellular Ca2+, was observed when intracellular Na+ was raised by inhibiting the Na/K pump with ouabain. These results do not provide evidence for Na/Mg exchange in heart cells, but they suggest that Ca2+ can modulate [Mg2+]i. In addition, removing extracellular Na+ caused a decrease in intracellular pH (pH(i)), as measured by pH-sensitive microelectrodes, and this acidification was attenuated when Ca2+ was also removed from the solution. These results suggest that Ca" and H+ interact intracellularly. Since changes in the Na+ gradient can also alter pH(i), we questioned whether pH can modulate [Mg2+]i. pH(i) was manipulated by the NH4Cl prepulse method. NH4+-evoked changes in pH(i), as measured by the fluorescent indicator BCECF, were accompanied by opposite changes in [Mg2+](i); [Mg2+]i changed by - 0. 16 mM/unit pH. These NH4+-evoked changes in [Mg2+]i were not caused by movements of Mg2+ or Ca2+ across the sarcolemma or by changes in cytosolic Ca2+. Additionally, pH(i) was manipulated by changing extracellular pH (pH(o)). When pH(o) was decreased from 7.4 to 6.3, pH(i) decreased by 0.64 units and [Mg2+]i increased by 0.12 mM; in contrast, when pH. was raised from 7.4 to 8.3, pH(i) increased by 0.6 units and [Mg2+]i did not change significantly. The results of our investigations suggest that Ca2+ and H+ can modulate [Mg2+]i, probably by affecting cytosolic Mg2+ binding and/or subcellular Mg2+ transport and that such redistribution of intracellular Mg2+ may play an important role in Mg2+ homeostasis in cardiac cells. C1 DUKE UNIV,MED CTR,DEPT CELL BIOL,DIV PHYSIOL,BOX 3709,DURHAM,NC 27710. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. FU NHLBI NIH HHS [5T32-HL07101, HL17670, HL27105] NR 22 TC 23 Z9 23 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP 8 PY 1992 VL 114 IS 1-2 BP 97 EP 103 PG 7 WC Cell Biology SC Cell Biology GA JQ517 UT WOS:A1992JQ51700015 PM 1461262 ER PT J AU HADARI, YR TZAHAR, E NADIV, O ROTHENBERG, P ROBERTS, CT LEROITH, D YARDEN, Y ZICK, Y AF HADARI, YR TZAHAR, E NADIV, O ROTHENBERG, P ROBERTS, CT LEROITH, D YARDEN, Y ZICK, Y TI INSULIN AND INSULINOMIMETIC AGENTS INDUCE ACTIVATION OF PHOSPHATIDYLINOSITOL 3'-KINASE UPON ITS ASSOCIATION WITH PP185 (IRS-1) IN INTACT RAT LIVERS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID RECEPTOR TYROSINE KINASES; SIGNAL TRANSDUCTION; PROTEIN; PHOSPHORYLATION; SUBSTRATE; CELLS; H2O2; PURIFICATION; PI3-KINASE; 3-KINASE AB The major cytosolic substrate of the insulin receptor is a 185-kDa phosphoprotein (IRS-1) that contains multiple putative attachment sites for the p85-alpha regulatory subunit of phosphatidylinositol 3'-kinase (PI3K). To examine the possible interaction of pp185 with p85-alpha in vivo, we injected insulin or insulinomimetic agents (a combination of H2O2 and vanadate (H/V)) into the portal vein of anesthetized rats. In this model system, H/V treatment and, to a lesser extent, injection of insulin resulted in rapid and sustained tyrosine phosphorylation of multiple cellular proteins, including pp185/IRS-1. The latter was found to undergo specific association with the p85-alpha regulatory subunit of PI3K but not with two other proteins that contain src homology domains. As p85-alpha was not detectably phosphorylated on tyrosine residues and did not appear to interact directly with the insulin receptor, we conclude that tyrosine phosphorylation of pp185 promotes its association with p85-alpha and the catalytic subunit of PI3K. The recruitment of the holoenzyme may also involve its enzymatic activation and thus constitute an important step in the transduction of insulin signals. C1 WEIZMANN INST SCI,DEPT CLIN IMMUNOL,IL-76100 REHOVOT,ISRAEL. UNIV PENN,SCH MED,DEPT PATHOL,PHILADELPHIA,PA 19104. NIH,DIABET BRANCH,BETHESDA,MD 20892. RI YARDEN, YOSEF/K-1467-2012; OI Roberts, Charles/0000-0003-1756-5772 NR 28 TC 114 Z9 114 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1992 VL 267 IS 25 BP 17483 EP 17486 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300002 PM 1381348 ER PT J AU QURESHI, SA ALEXANDROPOULOS, K RIM, M JOSEPH, CK BRUDER, JT RAPP, UR FOSTER, DA AF QURESHI, SA ALEXANDROPOULOS, K RIM, M JOSEPH, CK BRUDER, JT RAPP, UR FOSTER, DA TI EVIDENCE THAT HA-RAS MEDIATES 2 DISTINGUISHABLE INTRACELLULAR SIGNALS ACTIVATED BY V-SRC SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; PHORBOL 12-MYRISTATE 13-ACETATE; NIH 3T3 CELLS; GENE-EXPRESSION; PHOSPHOLIPASE-D; EARLY RESPONSE; TRANSFORMATION; GTPASE; TRANSDUCTION; ONCOGENES AB v-Src activates promoters under the control of 12-O-tetradecanoylphorbol-13-acetate (TPA) response elements (TREs) and serum response elements (SREs) via two distinguishable intracellular signaling mechanisms. The induction of TRE- and SRE-mediated gene expression by v-Src could be distinguished by a differential sensitivity to depleting cells of protein kinase C (PKC) and to a dominant negative Raf-1 mutant. Thus, PKC depletion and the dominant negative Raf-1 mutant were able to distinguish two intracellular signaling mechanisms activated by v-Src. Both of these v-Src-induced intracellular signals were sensitive to a dominant negative mutant of Ha-Ras. These data suggest that Ha-Ras functions to coordinately regulate multiple intracellular signaling mechanisms activated by v-Src. C1 CUNY HUNTER COLL,INST BIOMOLEC STRUCT & FUNCT,NEW YORK,NY 10021. CUNY HUNTER COLL,DEPT BIOL SCI,NEW YORK,NY 10021. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NCI NIH HHS [CA46677]; NCRR NIH HHS [RRO-3037-03] NR 50 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1992 VL 267 IS 25 BP 17635 EP 17639 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300027 PM 1325443 ER PT J AU BIRD, GS OBIE, JF PUTNEY, JW AF BIRD, GS OBIE, JF PUTNEY, JW TI SUSTAINED CA(2+) SIGNALING IN MOUSE LACRIMAL ACINAR-CELLS DUE TO PHOTOLYSIS OF CAGED GLYCEROPHOSPHORYL-MYO-INOSITOL 4,5-BISPHOSPHATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM; 1,4,5-TRISPHOSPHATE; TRISPHOSPHATE; KINETICS; TETRAKISPHOSPHATE; PERMEABILITY; HEPATOCYTES; GLAND; CA-2+ AB In saponin-permeabilized mouse lacrimal acinar cells, glycerophosphoryl-myo-inositol 4,5-bisphosphate (GPIP2) activated the release of sequestered Ca2+ to the same extent as inositol 1,4,5-trisphosphate ((1,4,5)IP3) but with a potency about 1/10 that of (1,4,5)IP3. In lacrimal gland homogenates, [H-3]GPIP2 was metabolized to two compounds which upon anion exchange high performance liquid chromatography eluted at positions indicating that they were [H-3]GPIP and [H-3]GPIP3. The rate of metabolism of [H-3]GPIP2 was much slower than that of [H-3](1,4,5)IP3, and its rate of phosphorylation was less than 1% of that of [H-3] (1,4,5)IP3. In intact lacrimal cells, photolysis of a microinjected "caged" derivative of GPIP2, 1-(alpha-glycero-phosphoryl)-myo-inositol 4,5-bisphoshhate p4(5)-1-(2-nitrophenyl)ethyl ester, resulted in sustained activation of Ca2+ signaling; i.e. intracellular Ca2+ release followed by increased entry of Ca2+ across the plasma membrane. These findings indicate that caged GPIP2 should provide a useful tool for producing photolytically initiated, sustained activation of intracellular (1,4,5)IP3 receptors. They also provide strong support for the idea that sustained Ca2+ signaling can be achieved in lacrimal acinar cells by activation of intracellular receptors for (1,4,5)IP3 in the absence of stimulated production of inositol 1,3,4,5-tetrakisphoshate. RP NIEHS, CELLULAR & MOLEC PHARMACOL LAB, CALCIUM REGULAT SECT, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 21 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1992 VL 267 IS 25 BP 17722 EP 17725 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300039 PM 1325446 ER PT J AU GUO, NH KRUTZSCH, HC VOGEL, T ROBERTS, DD AF GUO, NH KRUTZSCH, HC VOGEL, T ROBERTS, DD TI INTERACTIONS OF A LAMININ-BINDING PEPTIDE FROM A 33-KDA PROTEIN RELATED TO THE 67-KDA LAMININ RECEPTOR WITH LAMININ AND MELANOMA-CELLS ARE HEPARIN-DEPENDENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUNCTIONAL-CHARACTERIZATION; INTEGRIN ALPHA-7-BETA-1; MALIGNANT MELANOCYTES; SULFATED GLYCOLIPIDS; SYNTHETIC PEPTIDE; THROMBOSPONDIN; GLYCOPROTEIN; ADHESION; EXPRESSION; MIGRATION AB A laminin-binding peptide (peptide G), predicted from the cDNA sequence for a 33-kDa protein related to the 67-kDa laminin receptor, specifically inhibits binding of laminin to heparin and sulfatide. Since the peptide binds directly to heparin and inhibits interaction of another heparin-binding protein with the same sulfated ligands, this inhibition is due to direct competition for binding to sulfated glycoconjugates rather than an indirect effect of interaction with the binding site on laminin for the 67-kDa receptor. Direct binding of laminin to the peptide is also inhibited by heparin. This interaction may result from contamination of the laminin with heparan sulfate, as binding is enhanced by the addition of substoichiometric amounts of heparin but inhibited by excess heparin and two heparin-binding proteins. Furthermore, laminin binds more avidly to a heparin-binding peptide derived from thrombospondin than to the putative receptor peptide. Adhesion of A2058 melanoma cells on immobilized peptide G is also heparin-dependent, whereas adhesion of the cells on laminin is not. Antibodies to the beta-1-integrin chain or laminin block adhesion of the melanoma cells to laminin but not to peptide G. Thus, the reported inhibition of melanoma cell adhesion to endothelial cells by peptide G may result from inhibition of binding of laminin or other proteins to sulfated glycoconjugate receptors rather than from specific inhibition of laminin binding to the 67-kDa receptor. C1 NCI,PATHOL LAB,BLDG 10,RM 2A33,BETHESDA,MD 20892. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 29 TC 31 Z9 32 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1992 VL 267 IS 25 BP 17743 EP 17747 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300043 PM 1387642 ER PT J AU PRICE, SR WELSH, CF HAUN, RS STANLEY, SJ MOSS, J VAUGHAN, M AF PRICE, SR WELSH, CF HAUN, RS STANLEY, SJ MOSS, J VAUGHAN, M TI EFFECTS OF PHOSPHOLIPID AND GTP ON RECOMBINANT ADP-RIBOSYLATION FACTORS (ARFS) - MOLECULAR-BASIS FOR DIFFERENCES IN REQUIREMENTS FOR ACTIVITY OF MAMMALIAN ARFS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHOLERA-TOXIN; ADENYLATE-CYCLASE; NUCLEOTIDE-BINDING; BOVINE BRAIN; REGULATORY COMPONENT; PROTEIN ACTIVATOR; GOLGI-COMPLEX; EXPRESSION; GENE; COFACTOR AB ADP-ribosylation factors (ARFs) are highly conserved approximately 20-kDa guanine nucleotide-binding proteins that were first identified based on their ability to stimulate the cholera toxin-catalyzed ADP-ribosylation of G(s-alpha) and thus activate adenylyl cyclase. Proteins with ARF activity have been characterized from different mammalian tissues and exhibited different requirements for activity, stability, and phospholipid. Based on molecular cloning and mRNA distribution, at least six mammalian ARFs, which fall into three classes, have been identified. To test whether individual ARFs might have different requirements for optimal activity, as judged by their ability to enhance cholera toxin ADP-ribosyltransferase activity, four ARFs from classes I, II, and III were produced as recombinant proteins in Escherichia coli and characterized. Recombinant bovine ARF 2 (rARF 2) and human ARF 3 (rARF 3) (class I), human ARF 5 (rARF 5, class II), and human ARF 6 (rARF 6, class III) differed in the effects of phospholipid and detergent on their ability to enhance cholera toxin activity; rARFs 2, 3, and 5 required dimyristoylphosphatidylcholine (DMPC) and cholate, whereas rARF 6 did not require phospholipid/detergent for activity. Further characterization of two of the more divergent ARFs (ARFs 2 and 6) showed that both exhibited guanosine 5'-O-(3-thio)triphosphate binding which was enhanced by DMPC/cholate. In the transferase assay, rARF 2 required approximately 4-mu-M GTP for half-maximal stimulation of toxin activity, whereas rARF 6 required 0.05-mu-M GTP. rARF 6 exhibited a delay in activation of toxin not detected with rARF 2 that may be related to a requirement for guanine nucleotide exchange and/or GTP binding. These findings are consistent with the conclusion that the highly conserved members of the ARF family have different requirements for optimal activity. C1 NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. NR 35 TC 39 Z9 39 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1992 VL 267 IS 25 BP 17766 EP 17772 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300047 PM 1517219 ER PT J AU TAKAHASHI, M KAWAMOTO, S ADELSTEIN, RS AF TAKAHASHI, M KAWAMOTO, S ADELSTEIN, RS TI EVIDENCE FOR INSERTED SEQUENCES IN THE HEAD REGION OF NONMUSCLE MYOSIN SPECIFIC TO THE NERVOUS-SYSTEM - CLONING OF THE CDNA-ENCODING THE MYOSIN HEAVY CHAIN-B ISOFORM OF VERTEBRATE NONMUSCLE MYOSIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; SMOOTH-MUSCLE; MESSENGER-RNAS; DICTYOSTELIUM-DISCOIDEUM; SYNTHETIC PEPTIDES; CELLULAR MYOSIN; DNA-SEQUENCE; GENE FAMILY; IDENTIFICATION; ACANTHAMOEBA AB The complete amino acid sequence of a vertebrate nonmuscle myosin heavy chain-B isoform (MHC-B, 1976 amino acids, 229 kDa) has been deduced by using cDNA clones from chicken brain libraries. The chicken nonmuscle MHC-B shows overall similarity in primary structure to other MHCs in the areas contributing to the ATP-binding site and actin-binding site. Similar to other nonsarcomeric MHC IIs, there is a short uncoiled tail sequence at the carboxyl terminus of the molecule. It is in the uncoiled tail sequence that the greatest number of differences in amino acids sequence between MHC-A and B were found, which allowed generation of isoform-specific antibodies. These antibodies were used to determine the relative content of MHC-A and MHC-B in various tissues. During the cloning of the cDNA encoding chicken brain MHC-B, we found a 63-nucleotide insertion encoding 21 amino acids located in the head region of the MHC near to the actin-binding site and a 30 nucleotide insertion encoding 10 amino acids near to the ATP-binding site. Analysis using S- 1 nuclease showed that both inserts are expressed in a tissue-dependent manner; mRNA containing the inserts is present in tissues of the nervous system, but is absent from other nonmuscle cells, which contain the noninserted isoform of MHC-B. Similar inserts were found in corresponding positions in human cerebellar mRNA. Antibodies raised against a peptide synthesized based on the 21 amino acid insert found in chickens recognize a MHC isoform in the same tissues that are enriched for the mRNA. These insertions appear to be a mechanism for generating additional MHC-B isoforms specific to the nervous system. C1 NIH,MOLEC CARDIOL LAB,BLDG 10,RM 8N-202,BETHESDA,MD 20892. RI Takahashi, Masayuki/D-8079-2012; OI Adelstein, Robert/0000-0002-8683-2144 NR 47 TC 124 Z9 124 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1992 VL 267 IS 25 BP 17864 EP 17871 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300060 PM 1355479 ER PT J AU JEANG, KT BERKHOUT, B AF JEANG, KT BERKHOUT, B TI KINETICS OF HIV-1 LONG TERMINAL REPEAT TRANSACTIVATION - USE OF INTRAGENIC RIBOZYME TO ASSESS RATE-LIMITING STEPS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNA POLYMERASE-II; TRANSCRIPTION FACTOR ATF; TAT GENE-PRODUCT; TRANSLATIONAL REGULATION; PREINITIATION COMPLEX; PROMOTER INTERACTIONS; INITIATION-COMPLEXES; RESPONSIVE REGION; BINDING PROTEIN AB We have examined, using self-cleaving ribozymes, the intracellular trans-activation kinetics of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) by viral protein Tat. Experiments were designed to effect a competition (during RNA chain elongation) between cleavage of a nascent RNA containing the Tat-responsive target sequence (TAR) and Tat interaction with the same TAR in the-process of LTR-trans-activation. We found that fast self-cleavage of nascent TAR-containing RNA abolished Tat trans-activation. Slowing the cleavage reaction kinetically rescued trans-activation. Based on our results, we conclude that the rate-limiting step in HIV-1 LTR trans-activation is the initial contact made between Tat/TAR/LTR rather than the promoter proximal pausing of RNA polymerases that are tethered to functional TAR. RP JEANG, KT (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 67 TC 40 Z9 41 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1992 VL 267 IS 25 BP 17891 EP 17899 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300063 PM 1517225 ER PT J AU FISHER, RJ KOIZUMI, S KONDOH, A MARIANO, JM MAVROTHALASSITIS, G BHAT, NK PAPAS, TS AF FISHER, RJ KOIZUMI, S KONDOH, A MARIANO, JM MAVROTHALASSITIS, G BHAT, NK PAPAS, TS TI HUMAN ETS1-ONCOPROTEIN - PURIFICATION, ISOFORMS, SH MODIFICATION, AND DNA SEQUENCE-SPECIFIC BINDING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONG TERMINAL REPEAT; TRANSCRIPTION FACTOR; CHLOROMETHYL KETONE; ACTIVITY INVITRO; LEUKEMIA-VIRUS; PROTO-ONCOGENE; ETS ONCOGENE; PROTEINS; GENE; ACTIVATION AB The human ETS1 proto-oncogene proteins have been isolated from the T-cell leukemia line, CEM, by immunoaffinity chromatography and their identity confirmed by NH2-terminal amino acid sequencing. Incubation of CEM cells with N(alpha)-P-tosyl-L-lysine chloromethyl ketone (TLCK) indicates that ETS proteins can be modified in their cellular context and that pretreatment of the cells with N-ethylmaleimide (NEM) protects ETS1 proteins from TLCK modification. These data show that ETS1 proteins can exist in at least two different states, -SH-available and -SH-protected. Renatured human ETS1 has DNA sequence-specific binding to the PEA3 (CAGGAAGT) motif. The ETS1.PEA3 complex can be observed by electrophoretic mobility shift assays (EMSA). Purified ETS1 retards a band which is exactly the same size as a complex that is retarded from nuclear extracts prepared from CEM cells. Reduced ETS1 is required to form the ETS1.PEA3 complex, however; modification of the ETS1 -SH groups by either NEM or by TLCK does not inhibit formation of the complex. The ETS1.PEA3 complex formed with TLCK-modified ETS1 has a slower mobility than the complex formed with unmodified ETS1. Zone sedimentation analysis of purified ETS1 indicates that it is the monomer of ETS1 which binds to the PEA3 oligonucleotide. C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. RP FISHER, RJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,CELLULAR BIOCHEM LAB,FREDERICK,MD 21702, USA. RI Fisher, Robert/B-1431-2009 FU NCI NIH HHS [N01-CO-74102] NR 43 TC 44 Z9 44 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1992 VL 267 IS 25 BP 17957 EP 17965 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300073 PM 1517230 ER PT J AU YONEDA, K HOHL, D MCBRIDE, OW WANG, M CEHRS, KU IDLER, WW STEINERT, PM AF YONEDA, K HOHL, D MCBRIDE, OW WANG, M CEHRS, KU IDLER, WW STEINERT, PM TI THE HUMAN LORICRIN GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYMERASE CHAIN-REACTION; EPIDERMAL ALPHA-KERATIN; CROSS-LINKED ENVELOPE; HUMAN INVOLUCRIN GENE; CORNIFIED ENVELOPE; CELL-ENVELOPE; THERMUS-AQUATICUS; DNA-POLYMERASE; FILAGGRIN; PROTEIN AB Loricrin is the major protein component of the cornified cell envelope of terminally differentiated mammalian epidermal (stratum corneum) cells. Using a specific human cDNA clone, we have isolated and characterized the human loricrin gene. We show that it has a very simple structure of a single intron of 1188 base pairs (bp) in the 5'-untranslated region; there are no introns in coding sequences. By use of rodent-human somatic cell hybrids, followed by in situ hybridization with a biotin-labeled genomic DNA clone, the single-copy gene maps to chromosome location 1q21. Polymerase chain reaction analyses of genomic DNAs from different individuals show that human loricrin consists of two allelic size variants, due to sequence variations in its second glycine loop domain, and these variants segregate in the human population by normal Mendelian mechanisms. Furthermore, there are multiple sequence variants within these two size class alleles due to various deletions of 12 bp (4 amino acids) in the major loop of this glycine loop domain. By use of a specific loricrin antibody, we show by immunogold electron microscopy that loricrin initially appears in the granular layer of human epidermis and forms composite keratohyalin granules with profilaggrin, but localizes to the cell periphery (cell envelope) of fully differentiated stratum corneum cells. C1 NIAMS,SKIN BIOL LAB,BLDG 10,RM 9N228,BETHESDA,MD 20892. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 42 TC 90 Z9 92 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1992 VL 267 IS 25 BP 18060 EP 18066 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300089 PM 1355480 ER PT J AU ADAMCZEWSKI, M PAOLINI, R KINET, JP AF ADAMCZEWSKI, M PAOLINI, R KINET, JP TI EVIDENCE FOR 2 DISTINCT PHOSPHORYLATION PATHWAYS ACTIVATED BY HIGH-AFFINITY IMMUNOGLOBULIN-E RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; PROTEIN-TYROSINE KINASE; MEDIATED SIGNAL TRANSDUCTION; NATURAL-KILLER-CELLS; FC-GAMMA RECEPTOR; T-CELL; ZETA-CHAIN; PHOSPHOLIPASE C-GAMMA-1; PHENYLARSINE OXIDE; HISTAMINE-RELEASE AB The high affinity receptor for immunoglobulin (Ig) E on mast cells, along with the antigen receptors on T and B cells and Fc receptors for IgG, belongs to a class of receptors which lack intrinsic kinase activity, but activate non-receptor tyrosine and serine/threonine kinases. Receptor engagement triggers a chain of signaling events leading from protein phosphorylation to activation of phosphatidylinositol-specific phospholipase C, an increase in intracellular calcium levels, and ultimately the activation of more specialized functions. IgE receptor disengagement leads to reversal of phosphorylation by undefined phosphatases and to inhibition of activation pathways. Here we show that phenylarsine oxide, a chemical which reacts with thiol groups and has been reported to inhibit tyrosine phosphatases, uncouples the IgE receptor-mediated phosphorylation signal from activation of phosphatidyl inositol metabolism, the increase in intracellular calcium levels, and serotonin release. Phenylarsine oxide inhibits neither the kinases (tyrosine and serine/threonine) phosphorylating the receptor and various cellular substrates nor, unexpectedly, the phosphatases responsible for the dephosphorylation following receptor disengagement. By contrast, it abolishes the receptor-mediated phosphorylation of phospholipase C-gamma-1, but not phospholipase C activity in vitro. Therefore the phosphorylation and activation of phospholipase C likely requires a phenylarsine oxide-sensitive element. Receptor aggregation thus activates at least two distinct phosphorylation pathways: a phenylarsine oxide-insensitive pathway leading to phosphorylation/dephosphorylation of the receptor and of various substrates and a sensitive pathway leading to phospholipase C-gamma-1 phosphorylation. RP ADAMCZEWSKI, M (reprint author), NIAID,MOLEC ALLERGY & IMMUNOL SECT,TWINBROOK 2 BLDG,RM 108,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 53 TC 56 Z9 56 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1992 VL 267 IS 25 BP 18126 EP 18132 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300099 PM 1325458 ER PT J AU RANDAZZO, PA NORTHUP, JK KAHN, RA AF RANDAZZO, PA NORTHUP, JK KAHN, RA TI REGULATORY GTP-BINDING PROTEINS (ADP-RIBOSYLATION-FACTOR, G(T), AND RAS) ARE NOT ACTIVATED DIRECTLY BY NUCLEOSIDE DIPHOSPHATE KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUANINE-NUCLEOTIDE-BINDING; ADENYLATE-CYCLASE; TRIPHOSPHATE CONFORMATION; TUMOR-METASTASIS; ESCHERICHIA-COLI; BOUND GDP; P21; CELLS; GS; RHODOPSIN AB The expression of nucleoside diphosphate kinase (NDK) genes has been implicated as a negative regulator of murine and human tumor metastases and is critical to proper development in Drosophilia melanogaster. Molecular mechanisms for the role(s) of NDK in these complex processes have not yet been elucidated, but several reports have suggested that these and many other signal transduction pathways may be activated by NDK acting directly on a regulatory GTP-binding protein(s). To test this hypothesis, we examined the ability of NDK to catalyze the phosphorylation of the GDP bound to the following three members of the superfamily of regulatory GTP-binding proteins: G(t), Ha-ras p21, and ARF. We have found no evidence to support the hypothesis that NDK can directly activate any GTP-binding protein. Rather, evidence is presented which clearly shows that all of the GTP formed upon incubation of GTP-binding proteins with NDK is the result of NDK utilizing free GDP as substrate. The GDP bound to the regulatory proteins is not a substrate for NDK under conditions in which free nucleotides are rapidly and efficiently phosphorylated. The importance of appropriate controls for dissociation of GDP from the regulatory proteins both during the NDK reaction and during the analysis of product is demonstrated. We believe there is currently no experimental evidence to support the hypothesis that NDK can directly activate a regulatory GTP-binding protein. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 48 TC 64 Z9 64 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1992 VL 267 IS 25 BP 18182 EP 18189 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM223 UT WOS:A1992JM22300107 PM 1325460 ER PT J AU GULNIK, S BALDWIN, ET TARASOVA, N ERICKSON, J AF GULNIK, S BALDWIN, ET TARASOVA, N ERICKSON, J TI HUMAN LIVER CATHEPSIN-D - PURIFICATION, CRYSTALLIZATION AND PRELIMINARY-X-RAY DIFFRACTION ANALYSIS OF A LYSOSOMAL-ENZYME SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE CATHEPSIN-D; ASPARTIC PROTEINASE; LYSOSOMAL ENZYME; PURIFICATION; CRYSTALLIZATION ID BREAST-CANCER CELLS; AMINO-ACID-SEQUENCE; ASPARTIC PROTEINASES; 1.8-A RESOLUTION; PORCINE PEPSIN; 3-DIMENSIONAL STRUCTURE; 2.3-A RESOLUTION; BOVINE CHYMOSIN; D ISOZYMES; SPLEEN C1 NCI,FCRDC,PRI DYNCORP,CTR BIOMED SUPERCOMP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NCI,FCRDC,ABL BRP,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 46 TC 24 Z9 24 U1 2 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 5 PY 1992 VL 227 IS 1 BP 265 EP 270 DI 10.1016/0022-2836(92)90696-H PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JN259 UT WOS:A1992JN25900021 PM 1522590 ER PT J AU AZARI, NP RAPOPORT, SI SALERNO, JA GRADY, CL GONZALEZAVILES, A SCHAPIRO, MB HORWITZ, B AF AZARI, NP RAPOPORT, SI SALERNO, JA GRADY, CL GONZALEZAVILES, A SCHAPIRO, MB HORWITZ, B TI INTERREGIONAL CORRELATIONS OF RESTING CEREBRAL GLUCOSE-METABOLISM IN OLD AND YOUNG-WOMEN SO BRAIN RESEARCH LA English DT Article DE HUMAN; AGING; GENDER; POSITRON EMISSION TOMOGRAPHY; CORRELATION; CEREBRAL METABOLISM ID POSITRON EMISSION TOMOGRAPHY; AGING HUMAN-BRAIN; TRANSMISSION MEASUREMENTS; COMPUTED-TOMOGRAPHY; RATES; INTERCORRELATIONS; PATTERN; REGIONS; ADULTS; AGE AB A correlational analysis of normalized (regional to whole-brain) regional cerebral metabolic rates for glucose obtained in the 'resting' state eyes covered, ears plugged) using [F-18]fluorodeoxyglucose, demonstrated differences between old and young women in patterns of functional associations. Fifteen healthy young (age < 40 years) and 17 healthy old women (age > 64 years) were scanned with a Scanditronix PC1024-7B tomograph. The brain was divided into 65 regions of interest. The old women had fewer and less positive correlations between pairs of metabolic ratios in the frontal and parietal cortices. The results suggest an age-related reduction in frontal and parietal functional interactions in the 'resting' state that is consistent with a prior correlation analysis using a low resolution ECAT II scanner on young and old men. Reduced functional interactions may reflect age-related cognitive changes. RP AZARI, NP (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C414,BETHESDA,MD 20892, USA. NR 59 TC 43 Z9 43 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 4 PY 1992 VL 589 IS 2 BP 279 EP 290 DI 10.1016/0006-8993(92)91288-P PG 12 WC Neurosciences SC Neurosciences & Neurology GA JN182 UT WOS:A1992JN18200012 PM 1393596 ER PT J AU BECZKOWSKA, IW BOWEN, WD BODNAR, RJ AF BECZKOWSKA, IW BOWEN, WD BODNAR, RJ TI CENTRAL OPIOID RECEPTOR SUBTYPE ANTAGONISTS DIFFERENTIALLY ALTER SUCROSE AND DEPRIVATION-INDUCED WATER-INTAKE IN RATS SO BRAIN RESEARCH LA English DT Article DE SUCROSE INTAKE; DEPRIVATION-INDUCED WATER INTAKE; OPIOID RECEPTOR SUBTYPE; NALTREXONE; NOR-BINALTORPHAMINE; BETA-FUNALTREXAMINE; [D-ALA2,LEU5,CYS6]-ENKEPHALIN; NALTRINDOLE; NALOXONAZINE ID KAPPA-OPIATE RECEPTOR; NOR-BINALTORPHIMINE; FOOD-INTAKE; NONDEPRIVED RATS; PUTATIVE REINFORCERS; BETA-FUNALTREXAMINE; BEHAVIORAL-ANALYSIS; INGESTIVE BEHAVIOR; SELECTIVE AGONISTS; FLUID CONSUMPTION AB The present study compared the effectiveness of centrally-administered opioid receptor subtype antagonists to inhibit intake of either a 10% sucrose solution under ad libitum conditions, or water following 24 h of water deprivation. Full dose-response functions were evaluated over a 1 h period for the following antagonists: naltrexone (general: 1-50-mu-g), nor-binaltorphamine (Nor-BNI, kappa: 1-20-mu-g), beta-funaltrexamine (beta-FNA, mu: 1-20-mu-g), naltrindole (delta-2: 1-20-mu-g), [D-Ala2, Leu5, Cys6]-enkephalin (DALCE, delta-1: 10-40-mu-g) and naloxonazine (mu-1: 10-50-mu-g). Naltrexone significantly and dose-dependently inhibited both sucrose intake (64-67%) and deprivation-induced water intake (53-67%). Nor-BNI significantly and dose-dependently inhibited sucrose intake (53-55%), but failed to significantly affect (28%) deprivation-induced water intake. beta-FNA significantly and dose-dependently inhibited both sucrose intake (31-34%) and deprivation-induced water intake (36-50%). Naltrindole failed to significantly alter either sucrose intake (24%) or deprivation-induced water intake (16%). Whereas DALCE significantly, but transiently (15-20 min) inhibited sucrose intake (28%), it failed to significantly alter deprivation-induced water intake (14%). Naloxonazine significantly, but transiently (5-10 min) stimulated sucrose intake at low doses (26%), but non-significantly reduced sucrose intake at higher doses (20%). Naloxonazine failed to significantly alter deprivation-induced water intake (16% reduction). These data indicate that whereas the kappa and mu-2 binding sites participate in the opioid modulation of sucrose intake, the mu-2 binding site participates in the opioid modulation of deprivation-induced water intake. C1 CUNY QUEENS COLL,DEPT PSYCHOL & NEUROPSYCHOL,DOCTORAL SUB PROGRAM,FLUSHING,NY 11367. NIDDK,MED CHEM LAB,RECEPTOR BIOCHEM & PHARMACOL UNIT,BETHESDA,MD 20892. FU NIDA NIH HHS [DA 04194, DA03776] NR 79 TC 73 Z9 74 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 4 PY 1992 VL 589 IS 2 BP 291 EP 301 DI 10.1016/0006-8993(92)91289-Q PG 11 WC Neurosciences SC Neurosciences & Neurology GA JN182 UT WOS:A1992JN18200013 PM 1327413 ER PT J AU STEELE, TD KATZ, JL RICAURTE, GA AF STEELE, TD KATZ, JL RICAURTE, GA TI EVALUATION OF THE NEUROTOXICITY OF NORMAL-METHYL-1-(4-METHOXYPHENYL)-2-AMINOPROPANE (PARA-METHOXYMETHAMPHETAMINE, PMMA) SO BRAIN RESEARCH LA English DT Note DE PARA-METHOXYMETHAMPHETAMINE; METHAMPHETAMINE; NEUROTOXICITY; AMPHETAMINE; SEROTONIN ID CENTRAL SEROTONERGIC NEURONS; LONG-LASTING DEPLETION; RAT-BRAIN; PARA-CHLOROAMPHETAMINE; METHYLENEDIOXYAMPHETAMINE MDA; MDMA; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; 3,4-METHYLENEDIOXYAMPHETAMINE; METHYLENEDIOXYMETHAMPHETAMINE; AMPHETAMINE AB These studies assessed the neurotoxic potential of N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine; PMMA), an amphetamine analog that has surfaced in the illicit drug market. Repeated subcutaneous injections of PMMA caused lasting, dose-related reductions in regional brain concentrations of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), and in the density of [H-3]paroxetine-labelled labelled 5-HT uptake sites. Comparison of the neurotoxic potential of PMMA to that of para-methoxyamphetamine (PMA) and 3,4-methylenedioxymethamphetamine (MDMA) showed that equivalent doses of PMMA and PMA (80 mg/kg) produced comparable depletions of 5-HT, but that these depletions were not as pronounced as those induced by a lower dose of MDMA (20 mg/kg). Striatal DA was not affected on a long-term basis by any of the ring-substituted amphetamines evaluated in this study. These data suggest that PMMA, like PMA and MDMA, produces long-term (possibly neurotoxic) effects on brain serotonin neurons, but that PMMA is less potent than MDMA as a 5-HT neurotoxin. Further, they raise concern over the illicit use of PMMA since humans could be more sensitive than rodents to the 5-HT neurotoxic effects of PMMA and related drugs. C1 NIDA,ADDICT RES CTR,PSYCHOBIOL LAB,BALTIMORE,MD 21224. RP STEELE, TD (reprint author), JOHNS HOPKINS UNIV,SCH MED,FRANCIS SCOTT KEY MED CTR,DEPT NEUROL,301 BAYVIEW DR,BALTIMORE,MD 21224, USA. FU NIDA NIH HHS [DA 06275] NR 30 TC 18 Z9 18 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 4 PY 1992 VL 589 IS 2 BP 349 EP 352 DI 10.1016/0006-8993(92)91298-S PG 4 WC Neurosciences SC Neurosciences & Neurology GA JN182 UT WOS:A1992JN18200022 PM 1382813 ER PT J AU CHIPEV, CC KORGE, BP MARKOVA, N BALE, SJ DIGIOVANNA, JJ COMPTON, JG STEINERT, PM AF CHIPEV, CC KORGE, BP MARKOVA, N BALE, SJ DIGIOVANNA, JJ COMPTON, JG STEINERT, PM TI A LEUCINE-]PROLINE MUTATION IN THE H1 SUBDOMAIN OF KERATIN-1 CAUSES EPIDERMOLYTIC HYPERKERATOSIS SO CELL LA English DT Article ID 1/KERATIN-10 INTERMEDIATE FILAMENTS; COILED-COIL; BULLOSA SIMPLEX; INVITRO; GENE; PHOSPHORYLATION; ABNORMALITIES; ORGANIZATION; HETERODIMER; ICHTHYOSES AB Epidermolytic hyperkeratosis is an autosomal dominant disorder affecting the structural integrity of the suprabasal layers of human epidermis. We have recently documented in one family linkage of the disease phenotype to the cluster of type II keratins. We have now identified a leucine-->proline amino acid substitution in the conserved H1 subdomain of keratin 1 that is present only in affected family members. Using a quantitative assay and electron microscopy with synthetic peptides, we show that, whereas the wild-type H1 peptide rapidly disassembles preformed keratin filaments in vitro, the mutant peptide does this far less efficiently. Therefore the mutation in keratin 1 is likely to cause defective keratin filaments and hence a defective cytoskeleton in the epidermal cells in vivo. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. RP CHIPEV, CC (reprint author), NIAMSD,SKIN BIOL BRANCH,BETHESDA,MD 20892, USA. NR 37 TC 237 Z9 239 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 4 PY 1992 VL 70 IS 5 BP 821 EP 828 DI 10.1016/0092-8674(92)90315-4 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JL663 UT WOS:A1992JL66300013 PM 1381288 ER PT J AU ROCKEN, M URBAN, JF SHEVACH, EM AF ROCKEN, M URBAN, JF SHEVACH, EM TI INFECTION BREAKS T-CELL TOLERANCE SO NATURE LA English DT Article ID STAPHYLOCOCCAL ENTEROTOXIN-B; STIMULATORY FACTOR-I; TRANSGENIC MICE; CLONAL-DELETION; MONOCLONAL-ANTIBODY; SELF-TOLERANCE; RECEPTOR; ANERGY; INDUCTION; REACTIVITY AB CLONAL deletion or clonal anergy establish tolerance in T cells that bear potentially autoreactive antigen receptors1-15. Here we report that concomitant infection with the nematode Nippostrongylus brasiliensis breaks an established T-cell tolerance induced by injection of mice with Staphylococcus enterotoxin B (SEB)16,17. CD4+ T cells from SEB-tolerant mice did not produce either interleukin-2 or interleukin-4 when challenged in vitro with SEB. N. brasiliensis infection of SEB-primed animals resulted in a normal expansion of SEB-tolerant CD4+V-beta-8+ T cells in vivo as well as an equivalent increase of SEB-reactive, interleukin-4-producing CD4+V-beta-8+ T cells both in SEB-tolerant and in normal animals. Thus, infection with N. brasiliensis circumvented the tolerance established with SEB. Activation of anergic, potentially autoreactive CD4+ T cells by infectious agents seems to be a major pathway for the initiation of autoimmune diseases15. Our results suggest that infectious agents may break tolerance in potentially autoreactive CD4+ T cells by activation of alternative reaction pathways. C1 USDA ARS,BELTSVILLE AGR RES CTR,INST LIVESTOCK & POULTRY SCI,HELMINTH DIS LAB,BELTSVILLE,MD 20705. RP ROCKEN, M (reprint author), NIAID,IMMUNOL LAB,BETHESDA,MD 20892, USA. OI Urban, Joseph/0000-0002-1590-8869 NR 29 TC 142 Z9 142 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 3 PY 1992 VL 359 IS 6390 BP 79 EP 82 DI 10.1038/359079a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JL662 UT WOS:A1992JL66200059 PM 1355854 ER PT J AU NICKLAS, JM PITT, B TIMMIS, G BRENEMAN, G JAFRI, SM DUVERNOY, WFC DAVIS, SW GOLDBERG, MJ BLAIR, J MANCINI, GBJ JOHNSON, T LUCKOFF, C HENRY, G WLODKOWSKI, MB CZAJKA, M REINSTEIN, D RICHARDS, J LEWIS, R DAVEY, DE MALLOTTE, K MOLL, A QUAIN, L THOMASMA, P SCHREIBER, S URSINY, E ROGERS, WJ ARCINIEGAS, JG BITTNER, V BULLE, TM CAVENDER, JB CHARLES, ED DELLITALIA, LJ HENZLOVA, MJ MACLEAN, WA PAPAPIETRO, SE PAINE, TD SALVIA, MF SHEFFIELD, LT STANLEY, AWH VANTASSEL, E TAYLOR, HA CARLISLE, K BAKER, A BLACKBURN, G BONVILLE, B BYNUM, K DERISO, S KERNS, D LAMBERT, N MERRITT, L NANCE, V REDDY, E ATKINS, F COX, M POULEUR, H ROUSSEAU, MF MELIN, J MARCHANDISE, B SCHROEDER, E AHN, S MCINTYRE, KM TOW, D PIETRO, D GILLIE, E SHARMA, GVRK WOODS, P DONDERO, MEC BROWN, R STRAUSS, W LOSCALZO, J SALEM, D KONSTAM, MA UDELSON, JE WEINSHEL, A GAASCH, W DOLAN, N HOSHINO, R LANE, C KELLY, S KILCOYNE, L KINAN, D METHERALL, J PARADISE, L TOLTSIS, H LEJEMTEL, TH FRISHMAN, WH WEXLER, J GALVAO, M MILLS, LA JONES, M KOHN, RM MOREY, PD FORTE, KE HONG, MJ MADDI, JL ZIZZI, JA BERNASKI, EJ ROBERTS, NA BONORA, MM CELANO, JA BANKS, LD MUFFOLETTO, EM RICH, S BRUNDAGE, BH SHANES, JG PAPP, MA MATHEW, J BERARDUCCI, L GHALI, JK COOPER, R DIERENFELDT, BJ STANFORD, S MUMBY, P DAVIDSON, S ADAMS, T PEPINE, CJ CONTI, CR MEHTA, JL LIMACHER, MC FELDMAN, RL GEISER, EA HILL, JA LAMBERT, CR PRIDA, X MCCOY, K MIRANDA, A NORVELL, NK GREEN, JR MILLER, AB PERCHALSKI, DL HANDBERG, E HALL, B JOHNSTONE, DE GARDNER, MJ MONTAGUE, TJ LALONDE, LD KLASSEN, GA TEO, KK CHANDLER, BM CAREW, B BLACK, S FRANCIS, M MARTIN, S YOUNG, JB PRATT, CM QUINONES, MA ROBERTS, R KINGRY, C GIBSON, D FOREMAN, C KOPELEN, H GALAN, A MILLER, L YANG, K MARKS, G FRANCIS, M KIRLIN, PC WILLIS, PW JONES, JW BAIRD, WM FRITZ, T PERRY, B MCNAMARA, R MURRAY, RH SCAFFIDI, LE BOICHOT, H SOLIS, N BACHMAN, C FOOY, C MCKAY, K VANDERPUY, M HINER, K WORDEN, E HEARNS, P COHN, JN KUBO, SH FRANCIS, GS PETERSON, C GOLDENBERG, IF MCBRIDE, JW BERMAN, D HESSION, W GOLDSMITH, SR PEDERSON, WR HOLMER, S BJERKEN, GK MONSON, K PEARSON, J OTOOLEBREHM, B MENSING, L BOURASSA, MG GOULET, C JOYAL, M GOSSELIN, G LABBE, M METHE, M BENJAMIN, H MORTIN, S LECLERC, D KRONENBERG, MW FRIESINGER, GC BYRD, BF CAMPBELL, WB NADEAU, JH SCHILLING, S HOWE, DM EDENS, TR BERNARD, YD BROWN, LA SMITH, RF KOSTIS, JB SHINDLER, DM LACY, CR SUMATHISENA KARSTENSEN, S WILLIAMS, J HILL, B WOOD, L STEINHAGEN, J JESSUP, M BROZENA, S VICTOR, M HAGAMAN, J CANNON, M MCDONOUGH, J LUHMANN, S SMITH, AL KELLY, J STINSON, D GREENBERG, B DEMOTS, H GROVER, J REINHART, S NAUMAN, D DUTTON, D GUILLOTTE, M SCHMIT, M CAPONE, RJ MCNULTY, C SHARMA, S SADANIANTZ, A GORKIN, L HANDSHAW, K ERIKSON, L LAMORE, C REDFERN, L RUBBERT, P TREMBLAY, D HOOD, WB LIANG, CS FITZPATRICK, PG RICHESON, JF ACCIARI, KJ DIVERS, LD STONE, TM FARRELL, MJ MILLER, KD MOORE, AW WELLINGTON, KL EASLEY, RM RYAN, GF BAROLD, S GILLESPIE, JA COVE, L ROACHE, MP MALCOLM, JM STEWART, DK KENNEDY, JW CALDWELL, JH MURRAY, JA HEGG, TD WALLACH, R CHAMUSCO, R KUDENCHUCK, P OLMSTEAD, S DASH, H GORHAM, J RESNICK, A CAHILL, L LETTERER, R KEMPF, T GARDNER, P DALQUIST, J OLSUFKA, M GREGORY, JJ BROCK, DC LAUER, R GREENE, A FISCHL, SJ SLAMA, R STEIN, E KALISCHER, A DIEHL, L FACCHINEI, S ROMANO, J OLEARY, E KIMBALL, G BROCK, L HERMAN, MV WEISS, MB KAY, RH EVANS, M LERRICK, K UNGER, C RIPA, S BLAKE, J REID, M BRAGA, D TREULIEB, N CUTRONE, T BENEDICT, C HOLLAND, OB BODOLA, F CAPPOLINO, D SHENG, WL CHAKRAVARTHY, S ENTEZAMI, AA SULLIVAN, C WU, CW DAVIS, CE HOSKING, JD BANGDIWALA, SI BARRETT, J GARCES, C KRAL, KM TORETSKY, ER YOUNGBLOOD, ME STEWART, D HAZARD, CJ WEINER, DH ADAMS, KF EKELUND, LG KO, WJ JARRAD, I WILLIAMS, G SHELTON, BJ JONES, D NELSON, JJ SMITH, V THORN, M PROBSTFIELD, J VERTER, J SCHRON, E SCHUMACKER, S DAVIS, P WEBSTER, E RAPAPORT, E BROWN, BW COHEN, LS HALPERIN, M PACKER, M WALTERS, L GUNNAR, R FRIEDEWALD, W YUSUF, S PITT, B DAVIS, CE HOOD, WB COHN, JN AF NICKLAS, JM PITT, B TIMMIS, G BRENEMAN, G JAFRI, SM DUVERNOY, WFC DAVIS, SW GOLDBERG, MJ BLAIR, J MANCINI, GBJ JOHNSON, T LUCKOFF, C HENRY, G WLODKOWSKI, MB CZAJKA, M REINSTEIN, D RICHARDS, J LEWIS, R DAVEY, DE MALLOTTE, K MOLL, A QUAIN, L THOMASMA, P SCHREIBER, S URSINY, E ROGERS, WJ ARCINIEGAS, JG BITTNER, V BULLE, TM CAVENDER, JB CHARLES, ED DELLITALIA, LJ HENZLOVA, MJ MACLEAN, WA PAPAPIETRO, SE PAINE, TD SALVIA, MF SHEFFIELD, LT STANLEY, AWH VANTASSEL, E TAYLOR, HA CARLISLE, K BAKER, A BLACKBURN, G BONVILLE, B BYNUM, K DERISO, S KERNS, D LAMBERT, N MERRITT, L NANCE, V REDDY, E ATKINS, F COX, M POULEUR, H ROUSSEAU, MF MELIN, J MARCHANDISE, B SCHROEDER, E AHN, S MCINTYRE, KM TOW, D PIETRO, D GILLIE, E SHARMA, GVRK WOODS, P DONDERO, MEC BROWN, R STRAUSS, W LOSCALZO, J SALEM, D KONSTAM, MA UDELSON, JE WEINSHEL, A GAASCH, W DOLAN, N HOSHINO, R LANE, C KELLY, S KILCOYNE, L KINAN, D METHERALL, J PARADISE, L TOLTSIS, H LEJEMTEL, TH FRISHMAN, WH WEXLER, J GALVAO, M MILLS, LA JONES, M KOHN, RM MOREY, PD FORTE, KE HONG, MJ MADDI, JL ZIZZI, JA BERNASKI, EJ ROBERTS, NA BONORA, MM CELANO, JA BANKS, LD MUFFOLETTO, EM RICH, S BRUNDAGE, BH SHANES, JG PAPP, MA MATHEW, J BERARDUCCI, L GHALI, JK COOPER, R DIERENFELDT, BJ STANFORD, S MUMBY, P DAVIDSON, S ADAMS, T PEPINE, CJ CONTI, CR MEHTA, JL LIMACHER, MC FELDMAN, RL GEISER, EA HILL, JA LAMBERT, CR PRIDA, X MCCOY, K MIRANDA, A NORVELL, NK GREEN, JR MILLER, AB PERCHALSKI, DL HANDBERG, E HALL, B JOHNSTONE, DE GARDNER, MJ MONTAGUE, TJ LALONDE, LD KLASSEN, GA TEO, KK CHANDLER, BM CAREW, B BLACK, S FRANCIS, M MARTIN, S YOUNG, JB PRATT, CM QUINONES, MA ROBERTS, R KINGRY, C GIBSON, D FOREMAN, C KOPELEN, H GALAN, A MILLER, L YANG, K MARKS, G FRANCIS, M KIRLIN, PC WILLIS, PW JONES, JW BAIRD, WM FRITZ, T PERRY, B MCNAMARA, R MURRAY, RH SCAFFIDI, LE BOICHOT, H SOLIS, N BACHMAN, C FOOY, C MCKAY, K VANDERPUY, M HINER, K WORDEN, E HEARNS, P COHN, JN KUBO, SH FRANCIS, GS PETERSON, C GOLDENBERG, IF MCBRIDE, JW BERMAN, D HESSION, W GOLDSMITH, SR PEDERSON, WR HOLMER, S BJERKEN, GK MONSON, K PEARSON, J OTOOLEBREHM, B MENSING, L BOURASSA, MG GOULET, C JOYAL, M GOSSELIN, G LABBE, M METHE, M BENJAMIN, H MORTIN, S LECLERC, D KRONENBERG, MW FRIESINGER, GC BYRD, BF CAMPBELL, WB NADEAU, JH SCHILLING, S HOWE, DM EDENS, TR BERNARD, YD BROWN, LA SMITH, RF KOSTIS, JB SHINDLER, DM LACY, CR SUMATHISENA KARSTENSEN, S WILLIAMS, J HILL, B WOOD, L STEINHAGEN, J JESSUP, M BROZENA, S VICTOR, M HAGAMAN, J CANNON, M MCDONOUGH, J LUHMANN, S SMITH, AL KELLY, J STINSON, D GREENBERG, B DEMOTS, H GROVER, J REINHART, S NAUMAN, D DUTTON, D GUILLOTTE, M SCHMIT, M CAPONE, RJ MCNULTY, C SHARMA, S SADANIANTZ, A GORKIN, L HANDSHAW, K ERIKSON, L LAMORE, C REDFERN, L RUBBERT, P TREMBLAY, D HOOD, WB LIANG, CS FITZPATRICK, PG RICHESON, JF ACCIARI, KJ DIVERS, LD STONE, TM FARRELL, MJ MILLER, KD MOORE, AW WELLINGTON, KL EASLEY, RM RYAN, GF BAROLD, S GILLESPIE, JA COVE, L ROACHE, MP MALCOLM, JM STEWART, DK KENNEDY, JW CALDWELL, JH MURRAY, JA HEGG, TD WALLACH, R CHAMUSCO, R KUDENCHUCK, P OLMSTEAD, S DASH, H GORHAM, J RESNICK, A CAHILL, L LETTERER, R KEMPF, T GARDNER, P DALQUIST, J OLSUFKA, M GREGORY, JJ BROCK, DC LAUER, R GREENE, A FISCHL, SJ SLAMA, R STEIN, E KALISCHER, A DIEHL, L FACCHINEI, S ROMANO, J OLEARY, E KIMBALL, G BROCK, L HERMAN, MV WEISS, MB KAY, RH EVANS, M LERRICK, K UNGER, C RIPA, S BLAKE, J REID, M BRAGA, D TREULIEB, N CUTRONE, T BENEDICT, C HOLLAND, OB BODOLA, F CAPPOLINO, D SHENG, WL CHAKRAVARTHY, S ENTEZAMI, AA SULLIVAN, C WU, CW DAVIS, CE HOSKING, JD BANGDIWALA, SI BARRETT, J GARCES, C KRAL, KM TORETSKY, ER YOUNGBLOOD, ME STEWART, D HAZARD, CJ WEINER, DH ADAMS, KF EKELUND, LG KO, WJ JARRAD, I WILLIAMS, G SHELTON, BJ JONES, D NELSON, JJ SMITH, V THORN, M PROBSTFIELD, J VERTER, J SCHRON, E SCHUMACKER, S DAVIS, P WEBSTER, E RAPAPORT, E BROWN, BW COHEN, LS HALPERIN, M PACKER, M WALTERS, L GUNNAR, R FRIEDEWALD, W YUSUF, S PITT, B DAVIS, CE HOOD, WB COHN, JN TI EFFECT OF ENALAPRIL ON MORTALITY AND THE DEVELOPMENT OF HEART-FAILURE IN ASYMPTOMATIC PATIENTS WITH REDUCED LEFT-VENTRICULAR EJECTION FRACTIONS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MYOCARDIAL-INFARCTION; CLINICAL-TRIALS AB Background. It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity. We studied the effect of an angiotensin-converting-enzyme inhibitor, enalapril, on total mortality and mortality from cardiovascular causes, the development of heart failure, and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure. Methods. Patients were randomly assigned to receive either placebo (n = 2117) or enalapril (n = 2111) at doses of 2.5 to 20 mg per day in a double-blind trial. Follow-up averaged 37.4 months. Results. There were 334 deaths in the placebo group, as compared with 313 in the enalapril group (reduction in risk, 8 percent by the log-rank test; 95 percent confidence interval, -8 percent [an increase of 8 percent] to 21 percent; P = 0.30). The reduction in mortality from cardiovascular causes was larger but was not statistically significant (298 deaths in the placebo group vs. 265 in the enalapril group; risk reduction, 12 percent; 95 percent confidence interval, -3 to 26 percent; P = 0.12). When we combined patients in whom heart failure developed and those who died, the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group (630 vs. 818; risk reduction, 29 percent; 95 percent confidence interval, 21 to 36 percent; P<0.001). In addition, fewer patients given enalapril died or were hospitalized for heart failure (434 in the enalapril group vs. 518 in the placebo group; risk reduction, 20 percent; 95 percent confidence interval, 9 to 30 percent; P<0.001). Conclusions. The angiotensin-converting-enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations, as compared with the rates in the group given placebo, among patients with asymptomatic left ventricular dysfunction. There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,CLIN TRIALS BRANCH,FED BLDG,RM 5C08,BETHESDA,MD 20892. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI 48109. UNIV ALABAMA,MED CTR,BIRMINGHAM,AL 35294. CATHOLIC UNIV LOUVAIN,B-1200 BRUSSELS,BELGIUM. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. YESHIVA UNIV ALBERT EINSTEIN COLL MED,WEILER HOSP,BRONX,NY 10461. BUFFALO GEN HOSP,BUFFALO,NY 14203. VET AFFAIRS MED CTR,BUFFALO,NY. UNIV ILLINOIS,SCH MED,CHICAGO,IL 60680. UNIV FLORIDA,GAINESVILLE,FL 32611. VET AFFAIRS MED CTR,GAINESVILLE,FL. VICTORIA GEN HOSP,HALIFAX B3H 2Y9,NS,CANADA. BAYLOR COLL MED,HOUSTON,TX 77030. MICHIGAN STATE UNIV,E LANSING,MI 48824. UNIV MINNESOTA,SCH MED,MINNEAPOLIS,MN 55455. MONTREAL HEART INST,MONTREAL H1T 1C8,QUEBEC,CANADA. VANDERBILT UNIV,MED CTR,SCH MED,NASHVILLE,TN 37232. UNIV MED & DENT NEW JERSEY,NEW BRUNSWICK,NJ 08903. UNIV MED & DENT NEW JERSEY,NEW BRUNSWICK,NJ. TEMPLE UNIV HOSP & MED SCH,PHILADELPHIA,PA 19140. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. BROWN UNIV,PROVIDENCE,RI 02912. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. UNIV WASHINGTON,MED CTR,SEATTLE,WA 98195. OVERLOOK HOSP,SUMMIT,NJ 07901. NEW YORK MED COLL,WESTCHESTER CTY MED CTR,VALHALLA,NY 10595. UNIV TEXAS,HLTH SCI CTR,NEUROHUMORAL LAB,HOUSTON,TX 77225. UNIV N CAROLINA,CTR COORDINATING,CHAPEL HILL,NC 27514. RI Friedewald, William/C-8034-2011 NR 11 TC 1758 Z9 1806 U1 2 U2 29 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 3 PY 1992 VL 327 IS 10 BP 685 EP 691 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA JL235 UT WOS:A1992JL23500003 ER PT J AU PETRAKOVA, E KOVAC, P GLAUDEMANS, CPJ AF PETRAKOVA, E KOVAC, P GLAUDEMANS, CPJ TI SYNTHESES OF SPECIFICALLY DEOXYGENATED METHYL ALPHA-ISOMALTOTRIOSIDES SO CARBOHYDRATE RESEARCH LA English DT Article ID ACID RELATED-COMPOUNDS; SECONDARY ALCOHOLS; EFFICIENT DEOXYGENATION; GENERAL PROCEDURE; ANTIBODIES; SUGARS; 2'-DEOXYNUCLEOSIDES; OLIGOSACCHARIDES; RIBONUCLEOSIDES; CONVERSION AB Specifically deoxygenated methyl alpha-isomaltotriosides were synthesized by the silver perchlorate-mediated condensation of a protected alpha-isomaltosyl chloride with suitably blocked derivatives of methyl alpha-D-glucopyranoside deoxygenated respectively at positions 2. 3, and 4, followed by deprotection. C1 NIDDKD,BETHESDA,MD 20892. NR 18 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP 2 PY 1992 VL 233 BP 101 EP 112 DI 10.1016/S0008-6215(00)90923-6 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA JP243 UT WOS:A1992JP24300008 PM 1332823 ER PT J AU TURNER, SH CHERNIAK, R REISS, E KWONCHUNG, KJ AF TURNER, SH CHERNIAK, R REISS, E KWONCHUNG, KJ TI STRUCTURAL VARIABILITY IN THE GLUCURONOXYLOMANNAN OF CRYPTOCOCCUS-NEOFORMANS SEROTYPE-A ISOLATES DETERMINED BY C-13 NMR-SPECTROSCOPY SO CARBOHYDRATE RESEARCH LA English DT Article ID CAPSULAR POLYSACCHARIDE; MONOCLONAL-ANTIBODIES; AIDS; GALACTOXYLOMANNAN; MENINGITIS; VARIANT; GATTII AB Cryptococcus neoformans, the etiologic agent of cryptococcal meningoencephalitis, produces glucuronoxylomannan (GXM) as the major capsule component. Purified GXMs obtained from eight serotype A isolates of C. neoformans were treated by ultrasonic irradiation and then 0-deacetylated prior to their comprehensive chemical analysis by GLC, GLC-MS, and C-13 NMR spectroscopy. The average xylose:mannose:glucuronic acid molar ratio of the eight isolates is 1.96+/-0.25:3.00:0.58+/-0.10. Methylation analyses and C-13 NMR spectroscopy show a general structure for GXM that is comprised of a linear (1 --> 3)-alpha-D-mannopyranan substituted with beta-D-Glc pA and with beta-D-Xyl p at 0-2. Variable quantities of unsubstituted (1 --> 3)-alpha-D-Man p were observed between the eight isolates studied. In several isolates some of the (I --> 3)-alpha-D-Man p residues are disubstituted with beta-D-Glc pA at 0-2 and with beta-D-Xyl p at 0-4; this type of substitution was not previously thought to occur in serotype A isolates. Heterogeneity, between isolates, in the disposition of the substituents along the mannopyranan backbone was revealed by C-13 NMR spectroscopy. The eight isolates, and three isolates previously studied, were each assigned to one of four distinct groups based on the C-13 NMR chemical shifts of the anomeric carbons. Six of the eleven isolates gave identical spectra (Group I). The six major anomeric resonances from Group I were assigned to specific glycosidic linkages present in GXM. The remaining five isolates gave more complex spectra that are indicative of additional linkages and comprise the remaining three groups. Three of these five isolates contain substantial amounts of linkages previously thought to be distinctive of serotypes B and C, i.e., Man p residues that are 4-O-glycosylated with beta-D-Xyl p. Methylation analyses only predicted an average repeating unit, whereas C-13 NMR spectroscopy demonstrated that GXM from each isolate may be categorized into four groups by the occurrence of distinct sequences of carbohydrate residues. C1 GEORGIA STATE UNIV,DEPT CHEM,ATLANTA,GA 30303. GEORGIA STATE UNIV,BIOL & CHEM SCI LAB,ATLANTA,GA 30303. CTR DIS CONTROL,DIV BACTERIAL & MYCOT DIS,ATLANTA,GA 30333. NIAID,BETHESDA,MD 20205. FU NIAID NIH HHS [AI31769] NR 47 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP 2 PY 1992 VL 233 BP 205 EP 218 DI 10.1016/S0008-6215(00)90932-7 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA JP243 UT WOS:A1992JP24300017 PM 1446309 ER PT J AU BHATTACHARJEE, AK KWONCHUNG, KJ GLAUDEMANS, CPJ AF BHATTACHARJEE, AK KWONCHUNG, KJ GLAUDEMANS, CPJ TI THE MAJOR CAPSULAR POLYSACCHARIDE OF CRYPTOCOCCUS-NEOFORMANS SEROTYPE-B SO CARBOHYDRATE RESEARCH LA English DT Note C1 NIH,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NR 2 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP 2 PY 1992 VL 233 BP 271 EP 272 DI 10.1016/S0008-6215(00)90942-X PG 2 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA JP243 UT WOS:A1992JP24300027 PM 1446311 ER PT J AU ADAMSON, PC BALIS, FM SMITH, MA MURPHY, RF GODWIN, KA POPLACK, DG AF ADAMSON, PC BALIS, FM SMITH, MA MURPHY, RF GODWIN, KA POPLACK, DG TI DOSE-DEPENDENT PHARMACOKINETICS OF ALL-TRANS-RETINOIC ACID SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID THERAPEUTIC ANTICANCER AGENTS; ACUTE PROMYELOCYTIC LEUKEMIA; 13-CIS-RETINOYL GLUCURONIDES; METABOLISM; ISOTRETINOIN; PLASMA; IDENTIFICATION; MONKEY; INVIVO; LIVER AB Background: Orally administered all-trans-retinoic acid (all-trans-RA) can induce remission in a high proportion of patients with acute promyelocytic leukemia. Purpose: To further define the drug's pharmacokinetics, a study of intravenous all-trans-RA was performed in rhesus monkeys. Methods: A total of nine monkeys received intravenous bolus injections of all-trans-RA. Three different doses (20, 50, and 100 mg/m2) were each tested in three monkeys. Blood samples for determination of all-trans-RA concentration were obtained prior to drug administration and at 5, 10, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 360, and 480 minutes after drug administration. Results: Plasma disappearance of all-trans-RA was characterized by three distinct phases: a brief, initial exponential decline, followed by a relative plateau in the disappearance curve (the duration of which was dose dependent), and finally a terminal exponential decay. This profile is consistent with a capacity-limited (saturable) elimination process. The first-order (terminal) half-life for all-trans-RA averaged 19 minutes, and the mean clearances were 77, 52, and 59 mL/min for the 20-, 50-, and 100-mg/m2 dose groups, respectively. The mean +/- SD Michaelis constant (K(m)) for the capacity-limited process was 3.2 +/- 1.9-mu-M. Conclusions: Peak plasma concentrations following oral administration of 45 mg/m2 all-trans-RA in humans approach the K(m) for the capacity-limited process; thus, the dose-dependent pharmacokinetics of all-trans-RA described here may occur within the clinically used dosage range. RP ADAMSON, PC (reprint author), NCI,DIV CANC TREATMENT,PEDIAT BRANCH,BLDG 10,RM 13N240,BETHESDA,MD 20892, USA. NR 25 TC 45 Z9 45 U1 0 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 2 PY 1992 VL 84 IS 17 BP 1332 EP 1335 DI 10.1093/jnci/84.17.1332 PG 4 WC Oncology SC Oncology GA JK698 UT WOS:A1992JK69800011 PM 1495103 ER PT J AU UENO, K OHYAMA, M LIM, DJ AF UENO, K OHYAMA, M LIM, DJ TI EXPRESSION OF SIALIC ACIDS IN THE DEVELOPING MURINE TUBOTYMPANUM SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE GLYCOCONJUGATES; LECTIN; HISTOCHEMISTRY; MICROWAVE IRRADIATION ID LECTINS AB Sialoglycoconjugates in the developing murine tubotympanum were characterized using lectin histochemistry with wheat germ agglutinin (WGA), Limax flavus agglutinin (LFA), Sambucus nigra agglutinin (SNA), Maackia amurensis agglutinin (MAA), peanut agglutinin (PNA), and neuraminidase treatment. WGA, LFA, MAA, and neuraminidase-PNA labeled epithelial goblet cells, glandular mucous cells, and cell surfaces of adult and newborn murine tubotympanum. SNA did not label any secretory components. PNA labeled secretory cells and cell surfaces of the fetal tubotympanum without neuraminidase treatment. After birth, these secretory cells and cell surfaces were labeled with PNA only after neuraminidase treatment. These results revealed that: Sialoglycoconjugates are produced from glandular mucous cells and epithelial goblet cells and are present on cell surfaces and within the mucous blanket; their terminal tri-saccharide linkage appears to be the sequence Neu5Ac(alpha2-3)Gal(beta 1-3)GalNAc; sialic acids appear before birth and gradually increase; terminal galactose residues are masked by sialic acids after birth. C1 NIDCD,DIV INTRAMURAL PROGRAM,BETHESDA,MD. RP UENO, K (reprint author), KAGOSHIMA UNIV,FAC MED,DEPT OTOLARYNGOL,8-35-1 SAKURAGAOKA,KAGOSHIMA 890,JAPAN. NR 11 TC 9 Z9 10 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD SEP PY 1992 VL 112 IS 5 BP 824 EP 830 DI 10.3109/00016489209137480 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA JP656 UT WOS:A1992JP65600013 PM 1456038 ER PT J AU HARMAN, SM BLACKMAN, MR AF HARMAN, SM BLACKMAN, MR TI GROWTH-HORMONE, IGF-I, GONADAL-STEROIDS, AND AGING SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE AGING; GONADAL STEROIDS; GROWTH HORMONE; IGF-I RP HARMAN, SM (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,ROOM 2B20,BALTIMORE,MD 21205, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD SEP PY 1992 VL 4 IS 3 BP 257 EP 259 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA JP608 UT WOS:A1992JP60800012 PM 1420412 ER PT J AU REITZ, MS GUO, HG OLESKE, J HOXIE, J POPOVIC, M READCONNOLE, E MARKHAM, P STREICHER, H GALLO, RC AF REITZ, MS GUO, HG OLESKE, J HOXIE, J POPOVIC, M READCONNOLE, E MARKHAM, P STREICHER, H GALLO, RC TI ON THE HISTORICAL ORIGINS OF HIV-1 (MN) AND (RF) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Letter ID HTLV-III; AIDS C1 NCI,TUMOR CELL BIOL LAB,BLDG 37,RM 6A09,BETHESDA,MD 20892. UNIV MED & DENT NEW JERSEY,DIV ALLERGY IMMUNOL & INFECT DIS,NEWARK,NJ 07103. HOSP UNIV PENN,PHILADELPHIA,PA 19104. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. NR 12 TC 13 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 1992 VL 8 IS 9 BP 1539 EP 1541 DI 10.1089/aid.1992.8.1539 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JW296 UT WOS:A1992JW29600001 PM 1457197 ER PT J AU GOLDING, H DIMITROV, DS BLUMENTHAL, R AF GOLDING, H DIMITROV, DS BLUMENTHAL, R TI LFA-1 ADHESION MOLECULES ARE NOT INVOLVED IN THE EARLY STAGES OF HIV-1 ENV-MEDIATED CELL-MEMBRANE FUSION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HTLV-III/LAV ENVELOPE; SYNCYTIA FORMATION; GLYCOPROTEIN; INFECTION; LINE AB A recently developed sensitive assay to examine the early stages of HIV-1 env-mediated cell fusion is based on the redistribution of fluorescent dyes between membranes and cytoplasm of adjacent cells, monitored by fluorescence video microscopy. This assay demonstrated that membrane fusion can occur under conditions where no syncytia are formed. Fusion started earlier than syncytia formation and was not very sensitive to HIV-1 env+/CD4+ cell ratios. In the current study, this assay was used to determine the role of LFA-1 in HIV-1 env-mediated membrane fusion and syncytia formation. CD4- LFA-1- Epstein-Barr virus transformed lines from two leukocyte adhesion deficiency patients were infected with recombinant vaccinia expressing gp120/41 (HIV-IIIB), and cocultured with CD4+ subclones of the human T cell line CEM, which were generated by chemical mutagenesis and express either normal (LFA-1+), or low levels of LFA-1 (LFA-1lo). It was found that the LFA-1lo T-cell clone formed much smaller and fewer syncytia compared to the LFA-1+ subclones, but both clones fused equally well with the gp120/41 expressing LFA-1 B cells as monitored by redistribution of fluorescent dyes. Furthermore, monoclonal antibodies against the LFA-1 molecules reduced the number of syncytia formed but had no effect on membrane fusion. These findings demonstrate that the adhesion molecule LFA-1 does not play a crucial role in the early events of HIV-1 env-mediated cell membrane fusion, but may contribute to the later events leading to giant cell formation. C1 NCI,LMMB,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. RP GOLDING, H (reprint author), FDA,CTR BIOL EVALUAT & RES,DIV VIROL,BLDG 29A,ROOM 2C15,HFB-555,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 15 TC 16 Z9 16 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 1992 VL 8 IS 9 BP 1593 EP 1598 DI 10.1089/aid.1992.8.1593 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JW296 UT WOS:A1992JW29600010 PM 1457205 ER PT J AU KORPI, ER PAIVARINTA, P ABI-DARGHAM, A HONKANEN, A LARUELLE, M TUOMINEN, K HILAKIVI, LA AF KORPI, ER PAIVARINTA, P ABI-DARGHAM, A HONKANEN, A LARUELLE, M TUOMINEN, K HILAKIVI, LA TI BINDING OF SEROTONERGIC LIGANDS TO BRAIN MEMBRANES OF ALCOHOL-PREFERRING AA AND ALCOHOL-AVOIDING ANA RATS SO ALCOHOL LA English DT Article DE 5-HT RECEPTORS; [H-3]5-HT; [H-3]KETANSERIN; [H-3]LY278584; SELECTIVE BREEDING; AA AND ANA RATS; VOLUNTARY ALCOHOL CONSUMPTION ID RECEPTOR-BINDING; CEREBRAL-CORTEX; ETHANOL; DOPAMINE; 5-HYDROXYTRYPTAMINE; ANTAGONIST; MONOAMINES; STRAINS; LINES; ACID AB The alcohol-preferring AA rats have higher concentration of 5-hydroxytryptamine (5-HT) in the brain than the alcohol-avoiding ANA rats. In the present study, the 5-HT1, 5-HT2, and 5-HT3 receptors were studied with [H-3]5-HT, [H-3]ketanserin, and [H-3]LY278584, respectively, in membrane homogenates from different brain regions of both rat lines using in vitro binding assays. No differences in the 5-HT1, and 5-HT2 receptor binding in the brainstem, hippocampus, frontal cortex, and hypothalamus or in the 5-HT3 receptor binding in the nucleus accumbens, amygdala, hippocampus, and frontal cortex were observed between the ethanol-naive animals of the rat lines. In rats given the opportunity to voluntarily consume alcohol, there was a tendency to increase 5-HT1 binding in the ANA rats, which tendency was, however, also found in their ethanol-naive controls subjected to the same handling and behavioral tests as the ethanol-experienced animals. The results do not, however, indicate that any genetic modifications of the 5-HT receptor-binding sites have occurred in the process of the selective breeding of AA and ANA rats for alcohol preference and avoidance, respectively. C1 ALKO LTD, RES LABS, HELSINKI, FINLAND. ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, CLIN BRAIN DISORDERS BRANCH, WASHINGTON, DC 20032 USA. UNIV HELSINKI, DEPT PHYSIOL, SF-00100 HELSINKI 10, FINLAND. NR 41 TC 35 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 EI 1873-6823 J9 ALCOHOL JI Alcohol PD SEP-OCT PY 1992 VL 9 IS 5 BP 369 EP 374 DI 10.1016/0741-8329(92)90034-8 PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA JP892 UT WOS:A1992JP89200005 PM 1418660 ER PT J AU LANCASTER, FE SPIEGEL, KS AF LANCASTER, FE SPIEGEL, KS TI SEX-DIFFERENCES IN PATTERN OF DRINKING SO ALCOHOL LA English DT Article DE ALCOHOL; ETHANOL; SEX DIFFERENCES; PATTERN OF DRINKING ID VOLUNTARY BEER DRINKING; ALCOHOL-DEHYDROGENASE ACTIVITY; ETHANOL PREFERENCE; OFFSPRING GROWTH; PREGNANT RATS; CONSUMPTION; WOMEN; BRAIN; METABOLISM; STRAINS AB Drinking patterns of male and female Long-Evans rats were compared during a 15-day drinking period. All animals were tested for preference for alcohol for 24 h during which food, water, and beer containing 5% ethanol were freely available. Animals drinking 50 ml or more of beer were chosen for the experiments. On days 1-5, animals were offered food, water, and beer containing 5% ethanol (v/v). On days 6-15, the concentration of ethanol in the beer was doubled to 10% (v/v). Preference ratios (beer/total fluid) were higher for females than males, and females consumed more grams of alcohol per unit of body weight. When alcohol concentration was doubled, females increased alcohol intake (g/kg), while males tended to titrate alcohol intake to levels consumed at 5% concentration. Female patterns of drinking differed from male patterns of drinking. C1 TEXAS WOMANS UNIV,DEPT BIOL,HOUSTON,TX 77030. RP LANCASTER, FE (reprint author), NIAAA,DIV BASIC RES,NEUROSCI & BEHAV RES BRANCH,5600 FISHERS LANE,ROOM 16C-05,ROCKVILLE,MD 20857, USA. FU NIAAA NIH HHS [AA08009] NR 19 TC 97 Z9 98 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD SEP-OCT PY 1992 VL 9 IS 5 BP 415 EP 420 DI 10.1016/0741-8329(92)90041-8 PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA JP892 UT WOS:A1992JP89200012 PM 1418667 ER PT J AU BIANCHINE, PJ RUSSO, TA AF BIANCHINE, PJ RUSSO, TA TI THE ROLE OF EPIDEMIC INFECTIOUS-DISEASES IN THE DISCOVERY OF AMERICA SO ALLERGY PROCEEDINGS LA English DT Article AB As the world prepares to celebrate the quincentennial events surrounding the discovery of the New World by Christopher Columbus in 1492, a particular interest regarding the influence of epidemic infectious diseases on the history of the conquest of America has emerged. Contrary to popular belief it was not the European guns or fierce soldiers that conquered the native Americans, but instead it was the common childhood illnesses brought from the Old World by the European conquistadors. Diseases such as smallpox, measles, and typhus annihilated most of the American native populations. Devastating epidemics resulted throughout the New World. We will review the consequences of introducing new infectious agents into a nonimmune population, discuss the major pathogens that were imported from the Old World, and focus on how these diseases may have affected the aboriginal depopulation of the Americas. RP BIANCHINE, PJ (reprint author), NIAID,CLIN INVEST LAB,BLDG 10,ROOM 11C-216,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 15 Z9 16 U1 1 U2 8 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD SEP-OCT PY 1992 VL 13 IS 5 BP 225 EP 232 DI 10.2500/108854192778817040 PG 8 WC Allergy SC Allergy GA KA814 UT WOS:A1992KA81400002 PM 1483570 ER PT J AU COHEN, SG AF COHEN, SG TI 1ST IN ALLERGY .6. FEDERATION OF REGIONAL, STATE, AND LOCAL ALLERGY SOCIETIES SO ALLERGY PROCEEDINGS LA English DT Note RP COHEN, SG (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD SEP-OCT PY 1992 VL 13 IS 5 BP 269 EP 270 DI 10.2500/108854192778817031 PG 2 WC Allergy SC Allergy GA KA814 UT WOS:A1992KA81400010 PM 1483578 ER PT J AU REID, CL OTTO, CM DAVIS, KB LABOVITZ, A KISSLO, KB MCKAY, CR DIVER, DJ BERMAN, A SAFIAN, RD GROSSMAN, W COME, PC DOUGLAS, P MCKAY, RG SLATER, A WILLIAMS, DO DREW, TM CARNEVALE, R CIMINI, D HARDINK, D CANNON, P HOMMA, S BERKE, A KELLER, A ESCALA, E TRESGALLO, M BASHORE, TM DAVIDSON, CJ HARRISON, JK KISSLO, J KISSLO, K BRINKER, JA WEISS, JL RAQUENO, J DOWGER, B LAMBREW, CT CUTLER, J SZE, K TOOKER, N HOLMES, DR NISHIMURA, R REEDER, G MATHESON, SJ SCHREIFELS, S MEYER, L BLOCK, PC PALACIOS, IF WEYMAN, A BLOCK, EH PETITCLERC, R BROUILLETE, M SLATER, JN FEIT, F KRONZON, I ATTUBATO, MJ GINDEA, A BILYK, F KERN, MJ LABOVITZ, A STONNER, T MECHEM, C ALDERMAN, EL SCHNITTGER, I SCHWARZKOPF, A ROD, JL COMESS, K FERGUSON, J MASSUMI, A TREISTMAN, B HERNANDEZ, G WILANSKY, S HARLAN, M DEAN, LS BAXLEY, W NANDA, N KIRKLIN, JW SAENZ, C HELMCKE, FR MELUCH, FT BUCHBINDER, M PETERSON, K DITTRICH, H DAILY, E HILL, J MIRANDA, A PEPINE, C GEISER, E SCOTTFRANCO, E DEMARIA, AN WISENBAUGH, T BERK, M OBRIEN, M WEINER, BH PAPE, L BORBONE, ML NABEL, EG ARMSTRONG, WF GALEANA, A BUDA, A GALEANA, A RAHIMTOOLA, SH KAWANISHI, DT REID, C CHANDRARATNA, PAN MORRISON, E POWERS, ER SMUCKER, M GIBSON, R TEDESCO, C STEWART, DK ONEIL, W HAUSER, A DUDLETS, P PAVILEDES, G MARGULIS, A VANDERBERG, B WALLER, BF KENNEDY, JW GILLESPIE, MJ MICKEL, M SOLOMON, RE AF REID, CL OTTO, CM DAVIS, KB LABOVITZ, A KISSLO, KB MCKAY, CR DIVER, DJ BERMAN, A SAFIAN, RD GROSSMAN, W COME, PC DOUGLAS, P MCKAY, RG SLATER, A WILLIAMS, DO DREW, TM CARNEVALE, R CIMINI, D HARDINK, D CANNON, P HOMMA, S BERKE, A KELLER, A ESCALA, E TRESGALLO, M BASHORE, TM DAVIDSON, CJ HARRISON, JK KISSLO, J KISSLO, K BRINKER, JA WEISS, JL RAQUENO, J DOWGER, B LAMBREW, CT CUTLER, J SZE, K TOOKER, N HOLMES, DR NISHIMURA, R REEDER, G MATHESON, SJ SCHREIFELS, S MEYER, L BLOCK, PC PALACIOS, IF WEYMAN, A BLOCK, EH PETITCLERC, R BROUILLETE, M SLATER, JN FEIT, F KRONZON, I ATTUBATO, MJ GINDEA, A BILYK, F KERN, MJ LABOVITZ, A STONNER, T MECHEM, C ALDERMAN, EL SCHNITTGER, I SCHWARZKOPF, A ROD, JL COMESS, K FERGUSON, J MASSUMI, A TREISTMAN, B HERNANDEZ, G WILANSKY, S HARLAN, M DEAN, LS BAXLEY, W NANDA, N KIRKLIN, JW SAENZ, C HELMCKE, FR MELUCH, FT BUCHBINDER, M PETERSON, K DITTRICH, H DAILY, E HILL, J MIRANDA, A PEPINE, C GEISER, E SCOTTFRANCO, E DEMARIA, AN WISENBAUGH, T BERK, M OBRIEN, M WEINER, BH PAPE, L BORBONE, ML NABEL, EG ARMSTRONG, WF GALEANA, A BUDA, A GALEANA, A RAHIMTOOLA, SH KAWANISHI, DT REID, C CHANDRARATNA, PAN MORRISON, E POWERS, ER SMUCKER, M GIBSON, R TEDESCO, C STEWART, DK ONEIL, W HAUSER, A DUDLETS, P PAVILEDES, G MARGULIS, A VANDERBERG, B WALLER, BF KENNEDY, JW GILLESPIE, MJ MICKEL, M SOLOMON, RE TI INFLUENCE OF MITRAL-VALVE MORPHOLOGY ON MITRAL BALLOON COMMISSUROTOMY - IMMEDIATE AND 6-MONTH RESULTS FROM THE NHLBI BALLOON VALVULOPLASTY REGISTRY SO AMERICAN HEART JOURNAL LA English DT Article ID FACTORS DETERMINING RESTENOSIS; FOLLOW-UP; STENOSIS; VALVOTOMY; CATHETER; ECHOCARDIOGRAPHY; REPLACEMENT; ADULTS; AREA AB Echocardiographic data were analyzed in 555 patients undergoing mitral balloon commissurotomy (MBC). Patients were enrolled in the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry from 24 centers. There were 456 women and 99 men with a mean age of 54 years. Before MBC the two-dimensional echocardiographic variables of mitral valve thickness, mobility, calcification, and subvalvular disease were evaluated and assigned scores of 1 to 4. The mitral valve morphology score was related to mitral valve area (MVA) measured after MBC by cardiac catheterization. The leaflet mobility score was related to the immediate post-MBC MVA: 2.2 +/- 0.8 cm2 for grade 1, 1.9 +/- 0.7 cm2 for grade 2, 1.7 +/- 0.7 cm2 for grade 3, and 1.9 +/- 0.9 cm2 for grade 4 (p < 0.001). Results of the MVA after MBC showed a similiar relationship for each echocardiographic variable. The total morphology score (sum of the four variables) showed a weak relationship to MVA immediately after MBC (r = -0.24), which was persistent at 6 months after MBC (r = -0.25). Multiple regression analysis showed that the MVA after MBC is predicted by pre-MBC MVA (p < 0.001), left atrial size (p = 0.01), balloon diameter (p = 0.02), cardiac output (p = 0.004), and leaflet mobility (p = 0.01). The R2 of the model was 0.31 (p < 0.001). Total morphology score, leaflet thickness, calcification, and subvalvular disease were not important univariate or multivariate predictors of the results of MBC. These data suggest that although mitral valve morphology, particularly leaflet mobility, relates to MVA after MBC, other variables such as the severity and duration of disease are also important and are influenced by the larger balloon sizes used in the procedure. Mitral valve morphology should not be used alone in the selection of patients for MBC. C1 BETH ISRAEL HOSP,BOSTON,MA 02215. BROWN UNIV,PROVIDENCE,RI 02912. COLUMBIA UNIV,NEW YORK,NY 10027. DUKE UNIV,MED CTR,DURHAM,NC 27710. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. MAINE MED CTR,PORTLAND,ME 04102. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. UNIV WASHINGTON,SEATTLE,WA 98195. WILLIAM BEAUMONT HOSP,ROYAL OAK,MI 48072. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MONTREAL HEART INST,MONTREAL H1T 1C8,QUEBEC,CANADA. NYU,NEW YORK,NY 10003. ST LOUIS UNIV,ST LOUIS,MO 63103. STANFORD UNIV,STANFORD,CA 94305. SANTA CLARA VALLEY MED CTR,SAN JOSE,CA 95128. TEXAS HEART INST,HOUSTON,TX 77025. UNIV IOWA,IOWA CITY,IA 52242. ST VINCENT PROFESS BLDG,CORE PATHOL LAB,INDIANAPOLIS,IN. UNIV ALABAMA,BIRMINGHAM,AL 35294. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. UNIV FLORIDA,GAINESVILLE,FL 32611. UNIV KENTUCKY,LEXINGTON,KY 40506. UNIV MASSACHUSETTS,AMHERST,MA 01003. UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV SO CALIF,LOS ANGELES,CA 90089. NHLBI,BETHESDA,MD 20892. RP REID, CL (reprint author), UNIV CALIF IRVINE,IRVINE MED CTR,DIV CARDIOL,101 CITY DR,ORANGE,CA 92668, USA. FU NHLBI NIH HHS [N01-HV-78100] NR 27 TC 32 Z9 33 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 1992 VL 124 IS 3 BP 657 EP 665 DI 10.1016/0002-8703(92)90274-Y PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JL615 UT WOS:A1992JL61500016 PM 1514494 ER PT J AU MCAREAVEY, D FANANAPAZIR, L AF MCAREAVEY, D FANANAPAZIR, L TI ALTERED CARDIAC HEMODYNAMIC AND ELECTRICAL STATE IN NORMAL SINUS RHYTHM AFTER CHRONIC DUAL-CHAMBER PACING FOR RELIEF OF LEFT-VENTRICULAR OUTFLOW OBSTRUCTION IN HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIUM AB Dual-chamber (DDD) pacing relieves left ventricular (LV) outflow tract obstruction in patients with hypertrophic cardiomyopathy. The reduction in LV outflow gradient persists in some patients after cessation of pacing. Twelve-lead and signal-averaged electrocardiograms were obtained before and after 12 weeks of DDD pacing in 18 patients with obstructive hypertrophic cardiomyopathy to determine whether the altered hemodynamic state after chronic pacing is accompanied by electrical changes. Hemodynamic studies were performed at baseline and at follow-up. Signal-averaged electrocardiograms were obtained using a Corazonix Predictor and bidirectional filters at 25 Hz to a noise level of <0.5-mu-V. At follow-up, LV outflow tract gradients were reduced significantly during DDD pacing and with cessation of pacing in sinus rhythm by 56 +/- 10 and 47 +/- 10 mm Hg, respectively (p <0.001). There was no simple relation between changes in LV outflow tract gradient and in the electrocardiogram. For example, amplitude of the R wave in V5,6 was reduced by greater-than-or-equal-to 0.5 mv in 4 patients, unchanged in 12 and increased in 2. Similarly, the S wave in leads V1,2 was reduced in 7 patients, unchanged in 7 and increased in 4. The T wave became more negative (greater-than-or-equal-to 0.1 mv) in leads II, III, aVF and V5,6 in 13 patients and more positive in leads I and aVL in 12. The QRS was also altered by signal-averaged electrocardiographic criteria; duration of the total QRS and root-mean-square voltage of the QRS of the filtered Y axis increased (106 +/- 12 to 112 +/- 13 ms [p = 0.036] and 170 +/- 82 to 195 +/- 102-mu-V [p = 0.059], respectively). In conclusion, chronic DDD pacing significantly reduces obstruction to LV outflow, and after discontinuation of chronic DDD pacing, there is evidence of altered mechanical as well as electrical myocardial state. C1 NHLBI,CARDIOL BRANCH,CLIN ELECTROPHYSIOL LAB,BLDG 10,ROOM 7B-14,BETHESDA,MD 20892. NR 14 TC 27 Z9 27 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 1992 VL 70 IS 6 BP 651 EP 656 DI 10.1016/0002-9149(92)90207-F PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JK611 UT WOS:A1992JK61100016 PM 1510015 ER PT J AU MEDEIROS, LJ WEISS, LM AF MEDEIROS, LJ WEISS, LM TI ADRENAL-CORTICAL NEOPLASMS IN CHILDREN - REPLY SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Letter ID TUMORS C1 CITY HOPE NATL MED CTR, DEPT PATHOL, DUARTE, CA 91010 USA. RP NCI, PATHOL LAB, BETHESDA, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 1992 VL 98 IS 3 BP 382 EP 383 PG 2 WC Pathology SC Pathology GA JN580 UT WOS:A1992JN58000014 ER PT J AU BROWN, SA CHAMBLESS, LE SHARRETT, AR GOTTO, AM PATSCH, W AF BROWN, SA CHAMBLESS, LE SHARRETT, AR GOTTO, AM PATSCH, W TI POSTPRANDIAL LIPEMIA - RELIABILITY IN AN EPIDEMIOLOGIC FIELD-STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE LIPOPROTEINS, HDL CHOLESTEROL; LIPOPROTEINS, LDL CHOLESTEROL; TRIGLYCERIDES ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; IMPROVED LIPOLYTIC EFFICIENCY; DIETARY-FAT CLEARANCE; YOUNG MALE SURVIVORS; APOLIPOPROTEIN-A-I; MYOCARDIAL-INFARCTION; CHYLOMICRON REMNANTS; ENZYMATIC DETERMINATION; PLASMA TRIGLYCERIDE AB Ten subjects from the Forsyth County, North Carolina, and Washington County, Maryland, field centers in the Atherosclerosis Risk in Communities Study had two fat tolerance tests within a 10-day period from September 1988 to February 1989 to determine the reproducibility of markers for postprandial lipemia. No significant differences between visits were found in fasting mean plasma lipids, lipoproteins, and apolipoproteins. Postprandial triglycerides and retinyl palmitate were measured at 3.5 and 9.0 hours after the test meal in whole plasma. There were no significant differences in the mean levels of these analytes between visits. The correlation of triglycerides between repeat visits at 9.0 hours (r = 0.87) was stronger than in fasting samples (r = 0.67) or at 3.5 hours (r = 0.69). The mean plasma retinyl palmitate level at 3.5 hours was 15% higher than at the 9.0-hour level. The correlation of repeat measures of retinyl palmitate at 9.0 hours (r = 0.94) was much stronger than at 3.5 hours (r = 0.79). In conclusion, estimates of reliability in postprandial measurements of 9.0-hour triglycerides and retinyl palmitate levels were as strong as fasting lipid measurements of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and high density lipoprotein3 cholesterol. and both postprandial triglyceride measurements exceeded that of fasting triglyceride (r = 0.67). C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. UNIV N CAROLINA,DEPT BIOSTAT,CHAPEL HILL,NC 27514. NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892. RP BROWN, SA (reprint author), METHODIST HOSP,MAIL STOP A-601,6565 FANNIN AVE,HOUSTON,TX 77030, USA. FU NHLBI NIH HHS [HC NO1-HC-55016]; PHS HHS [27341] NR 46 TC 20 Z9 20 U1 1 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 1992 VL 136 IS 5 BP 538 EP 545 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KN667 UT WOS:A1992KN66700004 PM 1442717 ER PT J AU PATSCH, W SHARRETT, AR SORLIE, PD DAVIS, CE BROWN, SA AF PATSCH, W SHARRETT, AR SORLIE, PD DAVIS, CE BROWN, SA TI THE RELATION OF HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL AND ITS SUBFRACTIONS TO APOLIPOPROTEIN A-I AND FASTING TRIGLYCERIDES - THE ROLE OF ENVIRONMENTAL-FACTORS - THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ALCOHOL DRINKING; APOLIPOPROTEINS A; EXERCISE; LIPOPROTEINS; HDL; OBESITY; SMOKING; TRIGLYCERIDES ID IMPROVED LIPOLYTIC EFFICIENCY; HDL-CHOLESTEROL; ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; ENZYMATIC DETERMINATION; POSTPRANDIAL LIPEMIA; PHYSICAL-ACTIVITY; HEART-DISEASE; SEDENTARY MEN; WEIGHT-LOSS AB Cross-sectional analysis of four general representative populations of middle-aged adults in the United States in 1986-1989 provides estimates of the close relation of high density lipoprotein cholesterol (HDL cholesterol) to its major structural apolipoprotein (apolipoprotein A-I) and to fasting plasma triglyceride levels. HDL cholesterol differences of approximately 0.4 mg were associated with 1-mg differences in apolipoprotein A-I; differences of 20% in HDL cholesterol (reductions) were associated with triglyceride doublings. Variation in apolipoprotein A-I and triglyceride concentration together accounted for 66% of the population variance in HDL cholesterol. The uniformity of this pattern in the four race-sex groups studied suggests an important role of triglyceride-cholesterol transfer as a determinant of HDL cholesterol. The fundamental relations observed among HDL cholesterol, apolipoprotein A-I, and triglycerides were unaltered by levels of factors under personal volition. The volitional factors appeared to influence HDL cholesterol indirectly: Obesity and physical activity were affected primarily through their associations with triglycerides, and alcohol use and smoking through associations with apolipoprotein A-I. The association of alcohol use with elevated HDL cholesterol was attenuated in persons with greater body mass. C1 NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,FED BLDG,ROOM 2C08,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. METHODIST HOSP,HOUSTON,TX 77030. UNIV N CAROLINA,DEPT BIOSTAT,CHAPEL HILL,NC 27514. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 54 TC 34 Z9 34 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 1992 VL 136 IS 5 BP 546 EP 557 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KN667 UT WOS:A1992KN66700005 PM 1442718 ER PT J AU NAROD, SA PARRY, DM PARBOOSINGH, J LENOIR, GM RUTTLEDGE, M FISCHER, G ELDRIDGE, R MARTUZA, RL FRONTALI, M HAINES, J GUSELLA, JF ROULEAU, GA AF NAROD, SA PARRY, DM PARBOOSINGH, J LENOIR, GM RUTTLEDGE, M FISCHER, G ELDRIDGE, R MARTUZA, RL FRONTALI, M HAINES, J GUSELLA, JF ROULEAU, GA TI NEUROFIBROMATOSIS TYPE-2 APPEARS TO BE A GENETICALLY HOMOGENEOUS DISEASE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; POLYCYSTIC KIDNEY-DISEASE; HUMAN CHROMOSOME-22; TUBEROUS SCLEROSIS; LINKAGE ANALYSIS; POINT MUTATIONS; LENS OPACITIES; DNA MARKER; GENE; HETEROGENEITY AB Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome characterized by the development of vestibular schwannomas and other tumors of the nervous system, including cranial and spinal meningiomas, schwannomas, and ependymomas. The presence of bilateral vestibular schwannomas is sufficient for the diagnosis. Skin manifestations are less common than in neurofibromatosis type 1 (NF1; von Recklinghausen disease). The apparent clinical distinction between NF1 and NF2 has been confirmed at the level of the gene locus by linkage studies; the gene for NF1 maps to chromosome 17, whereas the gene for NF2 has been assigned (in a single family) to chromosome 22. To increase the precision of the genetic mapping of NF2 and to determine whether additional susceptibility loci exist, we have performed linkage analysis on 12 families with NF2 by using four polymorphic markers from chromosome 22 and a marker at the NF1 locus on chromosome 17. Our results confirm the assignment of the gene for NF2 to chromosome 22 and do not support the hypothesis of genetic heterogeneity. We believe that chromosome 22 markers can now be used for presymptomatic diagnosis in selected families. The NF2 gene is tightly linked to the D22S32 locus (maximum lod score 4.12; recombination fraction 0). A CA-repeat polymorphism at the CRYB2 locus was the most informative marker in our families (lod score 5.99), but because the observed recombination fraction between NF2 and CRYB2 was 10 cM, predictions using this marker will need to be interpreted with caution. C1 LUDWIG INST CANC RES, STOCKHOLM, SWEDEN. NCI, CLIN EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. NINCDS, NEUROEPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. INT AGCY RES CANC, F-69372 LYON, FRANCE. HOP NEUROL, DEPT NEUROSURG, F-69394 LYON 3, FRANCE. MCGILL CTR HUMAN GENET, MONTREAL, QUEBEC, CANADA. INST MED SPERIMENTALE, ROME, ITALY. MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02114 USA. KAROLINSKA HOSP, DEPT CLIN GENET, S-10401 STOCKHOLM 60, SWEDEN. MASSACHUSETTS GEN HOSP, NEUROGENET LAB, BOSTON, MA 02114 USA. UNIV LYON 1, F-69365 LYON 2, FRANCE. RI Haines, Jonathan/C-3374-2012 NR 42 TC 46 Z9 46 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1992 VL 51 IS 3 BP 486 EP 496 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA JJ828 UT WOS:A1992JJ82800005 PM 1496982 ER PT J AU QUEZADO, ZMN NATANSON, C AF QUEZADO, ZMN NATANSON, C TI SYSTEMIC HEMODYNAMIC ABNORMALITIES AND VASOPRESSOR THERAPY IN SEPSIS AND SEPTIC SHOCK SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE SEPTIC SHOCK; CYTOKINES; MYOCARDIAL DEPRESSION; VASOPRESSORS; CATECHOLAMINE ID TUMOR-NECROSIS-FACTOR; MYOCARDIAL DEPRESSANT SUBSTANCE; GRAM-NEGATIVE BACTEREMIA; CANINE MODEL; CARDIOVASCULAR DYSFUNCTION; VENTRICULAR DYSFUNCTION; CARDIAC DYSFUNCTION; ESCHERICHIA-COLI; NORMAL HUMANS; ENDOTOXIN RP QUEZADO, ZMN (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BLDG 10,BETHESDA,MD 20892, USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 49 TC 30 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 1992 VL 20 IS 3 BP 214 EP 222 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA JN139 UT WOS:A1992JN13900003 PM 1519602 ER PT J AU DAVIS, RO GOLDENBERG, RL BOOTS, L HOFFMAN, HJ COPPER, R CUTTER, GR DUBARD, MB CLIVER, SP SMITH, RK AF DAVIS, RO GOLDENBERG, RL BOOTS, L HOFFMAN, HJ COPPER, R CUTTER, GR DUBARD, MB CLIVER, SP SMITH, RK TI ELEVATED LEVELS OF MIDTRIMESTER MATERNAL SERUM ALPHA-FETOPROTEIN ARE ASSOCIATED WITH PRETERM DELIVERY BUT NOT WITH FETAL GROWTH-RETARDATION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE MATERNAL SERUM ALPHA-FETOPROTEIN; PRETERM DELIVERY; FETAL GROWTH RETARDATION; LOW BIRTH WEIGHT ID LOW-BIRTH-WEIGHT; RAISED SERUM; PREGNANCIES; TRIMESTER; VALUES AB OBJECTIVE: Our objective was to determine if the low birth weight associated with unexplained elevations of midtrimester maternal serum alpha-fetoprotein levels is due to prematurity or to fetal growth retardation. STUDY DESIGN: Rates of preterm delivery and fetal growth retardation were analyzed according to incremental maternal serum alpha-fetoprotein levels in 5555 women, predominantly white, who were screened for neural tube defects (group 1) and 843 women, predominantly black, with risk factors for low birth weight (group 2). Statistical methods included chi-2, t tests, analysis of variance, and regression analysis. RESULTS: In both groups increasing levels of maternal serum alpha-fetoprotein are significantly associated with preterm delivery but not with fetal growth retardation. The preterm delivery rate increased in each group from 8% at levels <0.5 multiples of the median to 18.1% (p < 0.001) at levels greater-than-or-equal-to 2.5 multiples of the median in group 1 and 28.1% (p = 0.01) in group 2. CONCLUSIONS: Women with unexplained elevations of maternal serum alpha-fetoprotein are at increased risk for preterm delivery but not fetal growth retardation. Because of the wide availability of maternal serum alpha-fetoprotein screening, women at increased risk for preterm delivery can be identified in the midtrimester of pregnancy. C1 NICHHD,BETHESDA,MD 20892. RP DAVIS, RO (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,DIV MATERNAL & FETAL MED,BIRMINGHAM,AL 35294, USA. FU NICHD NIH HHS [N01-HD-4-2811] NR 26 TC 27 Z9 29 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 1992 VL 167 IS 3 BP 596 EP 601 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA JN790 UT WOS:A1992JN79000005 PM 1382388 ER PT J AU BAUMRIND, S BENBASSAT, Y KORN, EL BRAVO, LA CURRY, S AF BAUMRIND, S BENBASSAT, Y KORN, EL BRAVO, LA CURRY, S TI MANDIBULAR REMODELING MEASURED ON CEPHALOGRAMS .2. A COMPARISON OF INFORMATION FROM IMPLANT AND ANATOMIC BEST-FIT SUPERIMPOSITIONS SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS LA English DT Article ID METALLIC IMPLANTS; QUANTITATION AB This study quantifies the differences in the perceived pattern of mandibular remodeling when two different methods are used to superimpose roentgenographic images of the mandible. Lateral cephalograms for a group of subjects with metallic implants of the Bjork type were superimposed twice; first on the metallic implants and then independently on mandibular anatomic structures according to a common "best fit" rule. In this article, we compare the between-superimposition differences in the perceived displacements of condyle, gonion, menton, pogonion, and Point B. Mean differences between the two superimpositional techniques were smaller than had been anticipated. For the 7-year time interval between 8.5 and 15.5 years, the largest mean differences between methods were 2.70 mm in the horizontal direction at condyle, 1.90 mm in the vertical direction at condyle, and 1.52 mm in the vertical direction at gonion. None of the other between-superimposition differences had a mean value in excess of 1 mm. The individual case variability between the two methods was, however, quite considerabie, a finding that we believe has bearing on the confidence that can be placed in individual case analyses in clinical orthodontics. A preliminary attempt has been made to represent and discuss the magnitude of this problem. C1 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT ORTHODONT,IL-91010 JERUSALEM,ISRAEL. NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. TRIMBLE NAVIGAT LTD,SUNNYVALE,CA. UNIV MURCIA,FAC MED,SCH STOMATOL,MURCIA,SPAIN. RP BAUMRIND, S (reprint author), UNIV CALIF SAN FRANCISCO,SCH DENT,DEPT GROWTH & DEV,CRANIOFACIAL RES INSTRUMENTAT LAB,SAN FRANCISCO,CA 94143, USA. FU NIDCR NIH HHS [DE07332, DE03598] NR 9 TC 13 Z9 15 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0889-5406 J9 AM J ORTHOD DENTOFAC JI Am. J. Orthod. Dentofac. Orthop. PD SEP PY 1992 VL 102 IS 3 BP 227 EP 238 DI 10.1016/S0889-5406(05)81057-1 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JM681 UT WOS:A1992JM68100007 PM 1510047 ER PT J AU MILLER, CJ VOGEL, P ALEXANDER, NJ SUTJIPTO, S HENDRICKX, AG MARX, PA AF MILLER, CJ VOGEL, P ALEXANDER, NJ SUTJIPTO, S HENDRICKX, AG MARX, PA TI LOCALIZATION OF SIV IN THE GENITAL-TRACT OF CHRONICALLY INFECTED FEMALE RHESUS MACAQUES SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; EPIDERMAL LANGERHANS CELLS; CERVICAL EPITHELIUM; TRANSMISSION; SECRETIONS; ANTIBODIES; TYPE-1; WOMEN; AIDS AB Despite the fact that human immunodeficiency virus (HIV) is transmitted primarily by sexual contact, the biology of the sexual transmission of HIV is poorly understood Simian immunodeficiency virus (SIV) can be transmitted to female rhesus macaques by placing cell-free virus in to the vaginal canal, and SIV can be isolated from the vaginal secretions of infected rhesus macaques. The authors examined the genital tracts from 16 chronically infected female rhesus macaques and localized SIV-infected cells using in situ hybridization and immunohistochemistry. SIV-infected cells were found in the genital tract of 13 of the 16 animals examined, and in most cases the SIV-infected cells were located in the submucosa of the cervix and vagina However SIV-infected cells were also found in the vaginal epithelium. SIV-infected cells were more common in sites of inflammation than in normal areas. These findings suggest that SIV gains access to genital tract secretions from the cervix and vaginal epithelium. C1 NICHHD,BETHESDA,MD 20892. RP MILLER, CJ (reprint author), UNIV CALIF DAVIS,CALIF RES PRIMATE RES CTR,DAVIS,CA 95616, USA. FU NCRR NIH HHS [RR 00169] NR 16 TC 79 Z9 79 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 1992 VL 141 IS 3 BP 655 EP 660 PG 6 WC Pathology SC Pathology GA JM679 UT WOS:A1992JM67900016 PM 1519670 ER PT J AU BARON, J HUANG, Z OERTER, KE BACHER, JD CUTLER, GB AF BARON, J HUANG, Z OERTER, KE BACHER, JD CUTLER, GB TI DEXAMETHASONE ACTS LOCALLY TO INHIBIT LONGITUDINAL BONE-GROWTH IN RABBITS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE GLUCOCORTICOIDS; GROWTH PLATE; EPIPHYSIS ID MESSENGER RIBONUCLEIC-ACID; SOMATOMEDIN ACTIVITY; COSTAL CHONDROCYTES; FACTOR-I; IGF-I; RAT; HORMONE; CARTILAGE; PLATE; GLUCOCORTICOIDS AB Excess glucocorticoid is a potent inhibitor of epiphysial growth. Several mechanisms have been suggested to explain this growth inhibition, including both direct local effects of glucocorticoid on the epiphysial growth plate and indirect systemic effects. Previous studies do not distinguish which of these proposed mechanisms is actually responsible for the growth suppression in vivo. To resolve this controversy, we developed a method for delivering glucocorticoid directly into the rabbit epiphysial growth plate and for accurately measuring the resulting epiphysial growth rate. Five-week-old male rabbits received a local infusion of dexamethasone phosphate (80 ng/mul, 1 mul/h) into one proximal tibial growth plate and an infusion of vehicle into the contralateral growth plate. Growth rate was determined by inserting metal pins into the bone immediately adjacent to the growth plate and measuring the change in distance between pins on serial radiographs. This method permitted growth rates to be measured over intervals as short as 3 days, with an error of approximately 5%. Local dexamethasone administration decreased proximal tibial growth rate by 77% compared with the contralateral vehicle-treated tibia (P < 0.0001). We conclude that excess glucocorticoid causes a rapid potent inhibition of growth by a direct local action on the growth plate. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP BARON, J (reprint author), NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892, USA. NR 28 TC 70 Z9 70 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1992 VL 263 IS 3 BP E489 EP E492 PN 1 PG 4 WC Physiology SC Physiology GA JP901 UT WOS:A1992JP90100034 PM 1415528 ER PT J AU CHOU, CL KNEPPER, MA AF CHOU, CL KNEPPER, MA TI INVITRO PERFUSION OF CHINCHILLA THIN LIMB SEGMENTS - SEGMENTATION AND OSMOTIC WATER PERMEABILITY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE DESCENDING LIMB; ASCENDING LIMB; HENLE LOOP; RAT ID MEDULLARY COLLECTING DUCT; RENAL TUBULE SEGMENTS; LONG-LOOPED NEPHRON; DESCENDING-LIMB; HENLES LOOP; SODIUM-CHLORIDE; FUNCTIONAL-HETEROGENEITY; FREEZE-FRACTURE; ASCENDING LIMB; UPPER PORTION AB The thin limb segments of the long loop of Henle are thought to play important roles in the urinary concentrating mechanism. In this study, we present new approaches to the identification, dissection, and in vitro perfusion of individual thin limb segments from all levels of the chinchilla renal medulla, including the deepest portions of the papilla. We have applied these techniques to the investigation of the osmotic water permeability along the chinchilla long loop of Henle. The results demonstrate that the osmotic water permeability of the thin descending limb is not uniformly high along its length, as previously thought, but that the distal 20% of the long-loop descending limb has a very low water permeability (almost-equal-to 50 mum/s). The transition to the low water permeability region of the thin descending limb is accompanied by a relatively abrupt change in morphology (increased cellularity and decreased diameter) that is readily perceptible in the perfused segments and even in the dissection dish. In contrast, the upper part of the chinchilla long-loop thin descending limb had an extremely high osmotic water permeability (>2,000 mum/s) as observed in other species. Thin ascending limbs from deep in the inner medulla had water permeabilities that were indistinguishable from zero, as previously found in thin ascending limbs from near the inner-outer medullary junction. The presence of a low-water-permeability portion of the long-loop thin descending limb in chinchilla may have important implications with regard to the inner medullary concentrating process. A relatively low osmotic water permeability (397 mum/s) was also found in the deep inner medullary portion of the thin descending limb from the rat. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,RM 6N307,BETHESDA,MD 20892. NR 40 TC 58 Z9 58 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1992 VL 263 IS 3 BP F417 EP F426 PN 2 PG 10 WC Physiology SC Physiology GA JP902 UT WOS:A1992JP90200102 PM 1415570 ER PT J AU GU, ZF JENSEN, RT MATON, PN AF GU, ZF JENSEN, RT MATON, PN TI A PRIMARY ROLE FOR PROTEIN KINASE-A IN SMOOTH-MUSCLE RELAXATION INDUCED BY ADRENERGIC AGONISTS AND NEUROPEPTIDES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE BETA-ADRENERGIC AGENTS; VASOACTIVE INTESTINAL PEPTIDE; CALCITONIN GENE-RELATED PEPTIDE; GLUCAGON; MUSCLE CONTRACTION; MUSCARINIC CHOLINERGIC RECEPTORS; ADENOSINE TRIPHOSPHATE; SODIUM NITROPRUSSIDE; ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE ID VASOACTIVE INTESTINAL PEPTIDE; GUINEA-PIG; CYCLIC 3',5'-PHOSPHOROTHIOATE; CELLS; CAMP; ADENOSINE; ANTAGONIST; RECEPTORS; NUCLEOTIDES; MECHANISMS AB Many studies suggest that smooth muscle relaxation caused by beta-adrenergic agents and various neuropeptides occurs as a result of an increase in cellular adenosine 3',5'-cyclic monophosphate (cAMP). However, the evidence is indirect, and furthermore does not demonstrate that an increase in cAMP is essential for mediating relaxation. To define more clearly the role of cAMP in receptor-mediated smooth muscle relaxation, we used a specific competitive antagonist of the action of cAMP on protein kinase A, (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS], and its S isomer, (S)-p-cAMPS, which functions as a cAMP agonist. In gastric smooth muscle cells from guinea pig, (S)-p-cAMPS caused a dose-related relaxation [50% inhibitory concentration (IC50) 86 +/- 59 nM]. Vasoactive intestinal peptide (VIP) produced smooth muscle cell relaxation (IC50 2.3 +/- 0.8 nM) through occupation of specific VIP receptors. (R)-p-cAMPS inhibited VIP-induced relaxation, with a rightward shift in the VIP dose-response curve, suggesting competitive antagonism. Furthermore, (R)-p-cAMPS inhibited relaxation induced by other agents that increase cellular cAMP (isoproterenol, calcitonin gene-related peptide, and glucagon) but not that induced by ATP or sodium nitroprusside. (R)-p-cAMPS had no effect on contraction stimulated by carbachol, cholecystokinin, or substance P. These data demonstrate that activation of protein kinase A is primarily responsible for mediating gastrin smooth muscle relaxation produced by adrenergic agents and various neuropeptides. C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NR 29 TC 21 Z9 21 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1992 VL 263 IS 3 BP G360 EP G364 PN 1 PG 5 WC Physiology SC Physiology GA JP901 UT WOS:A1992JP90100060 PM 1329527 ER PT J AU EICHENHOLZ, PW EICHACKER, PQ HOFFMAN, WD BANKS, SM PARRILLO, JE DANNER, RL NATANSON, C AF EICHENHOLZ, PW EICHACKER, PQ HOFFMAN, WD BANKS, SM PARRILLO, JE DANNER, RL NATANSON, C TI TUMOR-NECROSIS-FACTOR CHALLENGES IN CANINES - PATTERNS OF CARDIOVASCULAR DYSFUNCTION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CONTRACTILITY; LETHALITY ID HUMAN SEPTIC SHOCK; SYSTOLIC VOLUME RATIO; ESCHERICHIA-COLI; HUMAN SEPSIS; CACHECTIN; PERFORMANCE; ENDOTOXIN; PRESSURE; MODEL; INTERLEUKIN-1 AB Three groups of conscious canines were given different intravenous doses of human recombinant tumor necrosis factor (TNF) over 1 h, and the resulting cardiovascular abnormalities were examined for 10 days. As TNF dose increased [0 (controls), 30, 60, and 120 mug/kg body wt], the number of deaths increased (P < 0.025; 0 of 6, 1 of 8, 1 of 8, 4 of 8, number of deaths in each group, respectively). In all three groups receiving TNF, the mean left ventricular ejection fraction (LVEF) at 2 h after infusion decreased (P < 0.003) compared with controls. The group receiving the highest dose of TNF (1 20 mug/kg body wt) had the greatest decrease (P < 0.05) in LVEF from 0 to 2 h. At 8 h, all three groups receiving TNF had similar LVEF. In these three groups, other multiple measures of LV function at 8 h showed significant and similar decreases in cardiac contractility compared with controls. From 24 to 240 h, however, the time required for cardiac performance (LVEF) to return to normal was dose dependent (30 < 60 < 120 mug/kg body wt; P < 0.05). Canines receiving the lowest dose of TNF had near normal cardiac function (LVEF) at 24 h, whereas canines receiving the highest dose had persistent cardiac abnormalities at 240 h. Thus, at 8 h, the severity of cardiac dysfunction is independent of TNF dose, but the rate of onset and the duration of cardiac abnormality are markedly dependent of dose. These data show TNF decreases cardiac contractility within hours, and TNF dose is important in the timing and extent of cardiovascular changes and lethality. C1 NIH,DEPT CRIT CARE MED,CTR CLIN,BLDG 10 RM 7D43,BETHESDA,MD 20892. DEF NUCL AGCY,ARMED FORCES RADIOBIOL RES INST,BETHESDA,MD 20814. NR 31 TC 80 Z9 83 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1992 VL 263 IS 3 BP H668 EP H675 PN 2 PG 8 WC Physiology SC Physiology GA JP902 UT WOS:A1992JP90200006 PM 1415590 ER PT J AU PINN, VW AF PINN, VW TI WOMEN, RESEARCH, AND THE NATIONAL INSTITUTES OF HEALTH - COMMENTARY SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Note AB Women's physiologic and pathologic processes are capturing the national consciousness in what Dr. Bernadine Healy, the first woman director of the National Institutes of Health (NIH), has called a "new awakening." As she has pointed out, women have unique medical problems, but research focused on women's diseases has been inadequate. Our knowledge of too many common diseases is based almost entirely on studies of men. Unfortunately, most biomedical research has assumed women are just like men. Now, we witness a dramatic shift in perspective. Not just professional and scientific journals, but newspapers, television and radio productions, community and religious organizations, and even social conversations convey the urgency of women's health concerns. You have probably seen newspaper headlines and titles of journal articles like these: "Women's Reproductive Health: A Chronic Crisis," "The Gender Gap in Drug Tests," "Reproductive Problems Are a Major Killer of Women," "The Gender Gap in Heart Disease; Women Die Far More Frequently Than Men Who Undergo Artery-opening Procedures," "Rumble in the Ranks: Sexism May Be Fact of Medical Life, But Women Physicians Are Fighting Back," "Women's Health, Public Welfare," "Preventing Heart Disease in Women; Another Role For Aspirin," "America's Neglected Weapon: Its Educated Women." In fact, women's community, academic, and other advocacy groups have placed women's health at center stage. Moreover, the federal government is now also emphasizing women's health. The 1985 report of the Public Health Service Task Force on Women's Health Issues stated: "Biomedical and behavioral research should be expanded to ensure emphasis on conditions and diseases unique to, or more prevalent in, women in all age groups."1 Full implementation of this directive has only recently, however, become a priority of the medical and scientific communities. RP PINN, VW (reprint author), NIH,OFF RES WOMENS HLTH,BETHESDA,MD 20892, USA. NR 0 TC 14 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD SEP-OCT PY 1992 VL 8 IS 5 BP 324 EP 327 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA JR581 UT WOS:A1992JR58100011 PM 1419135 ER PT J AU LEONARD, HL LENANE, MC SWEDO, SE RETTEW, DC GERSHON, ES RAPOPORT, JL AF LEONARD, HL LENANE, MC SWEDO, SE RETTEW, DC GERSHON, ES RAPOPORT, JL TI TICS AND TOURETTES DISORDER - A 2-YEAR TO 7-YEAR FOLLOW-UP OF 54 OBSESSIVE-COMPULSIVE CHILDREN SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CLINICAL PHENOMENOLOGY; ADOLESCENTS; GILLES; CLOMIPRAMINE; PREVALENCE; METABOLISM; RELATIVES; FAMILY AB Objective: This study examined a hypothesized etiologic relationship between Tourette's disorder and obsessive-compulsive disorder. Method: Fifty-four children who bad initially participated in treatment protocols for obsessive-compulsive disorder (Tourette's disorder was an exclusionary criterion) were reevaluated 2-7 years later with a neurological examination and a structured interview to establish the presence or absence of tics and Tourette's disorder. The children's first-degree relatives (N=171) were also screened for tic disorders. Results: At baseline, 57% (N=31) of the patients bad lifetime histories of tics. At follow-up, 59% (N=32) bad lifetime histories of tics; eight of these (all males) met the criteria for Tourette's disorder (six bad developed the disorder, and two, it could be argued in retrospect, might have met the criteria at baseline). The patients with lifetime histories of tics had greater anxiety, a higher ratio of CSF S-hydroxyindoleacetic acid to homovanillic acid, and a younger age at onset of obsessive-compulsive disorder than those without tics. The patients with Tourette's disorder differed from other male patients only in having an earlier age at onset of obsessive-compulsive disorder. Of the first-degree relatives, 1.8% (N=3) bad Tourette's disorder, and 14% (N=24) had a tic disorder. Conclusions: Except for their earlier age at onset of obsessive-compulsive disorder, the patients with Tourette's disorder were indistinguishable from those without. The apparent high rate of tics and Tourette's disorder in the subjects and their relatives is consistent with the hypothesis that in some cases, obsessive-compulsive disorder and Tourette's disorder may be alternative manifestations of the same underlying illness. C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. RP LEONARD, HL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,RM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 38 TC 209 Z9 212 U1 3 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1992 VL 149 IS 9 BP 1244 EP 1251 PG 8 WC Psychiatry SC Psychiatry GA JK722 UT WOS:A1992JK72200020 PM 1503140 ER PT J AU SALIVE, ME CORNONIHUNTLEY, J LACROIX, AZ OSTFELD, AM WALLACE, RB HENNEKENS, CH AF SALIVE, ME CORNONIHUNTLEY, J LACROIX, AZ OSTFELD, AM WALLACE, RB HENNEKENS, CH TI PREDICTORS OF SMOKING CESSATION AND RELAPSE IN OLDER ADULTS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note ID QUITTING SMOKING; UNITED-STATES; CIGARETTE-SMOKING; DISEASE; AGE; SMOKERS; WOMEN; HELP; MEN; SEX AB We examined longitudinal changes smoking behavior among older adults in three community cohorts of the Established Populations for Epidemiologic Studies of the Elderly. Smoking prevalence declined from 15% at baseline to 9% during 6 years of follow-up. Annual smoking cessation and relapse rates were 10% and less than 1%, respectively. Interval diagnosis of myocardial infarction, stroke, or cancer increased subsequent smoking cessation but not relapse. Although smoking cessation around diagnosis is increased, primary prevention could yield greater benefits. C1 GRP HLTH COOPERAT PUGET SOUND,CTR HLTH STUDIES,SEATTLE,WA. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PREVENT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RP SALIVE, ME (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-0-2105, N01-AG-0-2107, N01-AG-0-2106] NR 25 TC 54 Z9 54 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 1992 VL 82 IS 9 BP 1268 EP 1271 DI 10.2105/AJPH.82.9.1268 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JK727 UT WOS:A1992JK72700014 PM 1503170 ER PT J AU LEBIHAN, D TURNER, R DOUEK, P PATRONAS, N AF LEBIHAN, D TURNER, R DOUEK, P PATRONAS, N TI DIFFUSION MR IMAGING - CLINICAL-APPLICATIONS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review ID ANISOTROPICALLY RESTRICTED DIFFUSION; INTRAVOXEL INCOHERENT MOTION; HUMAN-BRAIN; CEREBRAL-ISCHEMIA; SELF-DIFFUSION; NERVOUS-SYSTEM; WHITE MATTER; WATER; NMR; MUSCLE AB Water self-diffusion, a recently discovered source of contrast on MR images, has already shown promise for some clinical applications. Most studies have been of the brain, essentially for technical reasons. Diffusion is useful in distinguishing the different components of brain tumors (cystic regions, edema, necrosis) from the tumor core itself. Recent studies have shown that diffusion is anisotropic in brain white matter (i.e., dependent on the fiber tract's orientation in space), offering new insights into myelin disorders. Diffusion is also dramatically altered in the minutes following ischemic injury in the cat brain, which may have tremendous impact for the diagnosis and management of hyperacute stroke. With ultrafast acquisition schemes, diffusion imaging has also been used outside the CNS, for instance, in the eye and kidney. Future applications include diffusion-localized spectroscopy and temperature imaging. This article reviews recent progress in this field and suggests potential applications. C1 NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,DEPT RADIOL,WASHINGTON,DC 20007. RP LEBIHAN, D (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,RM 1C660,BETHESDA,MD 20892, USA. RI Turner, Robert/C-1820-2008 NR 60 TC 313 Z9 315 U1 2 U2 10 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1992 VL 159 IS 3 BP 591 EP 599 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JJ983 UT WOS:A1992JJ98300032 PM 1503032 ER PT J AU PREMKUMAR, A CHOW, CK CHOYKE, PL DOPPMAN, JL AF PREMKUMAR, A CHOW, CK CHOYKE, PL DOPPMAN, JL TI STRESS-INDUCED ADRENAL-HYPERPLASIA SIMULATING METASTATIC DISEASE - CT AND MR FINDINGS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. RP PREMKUMAR, A (reprint author), NIH,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1992 VL 159 IS 3 BP 675 EP 676 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JJ983 UT WOS:A1992JJ98300054 PM 1503051 ER PT J AU MOMOSE, H JAFFE, ES SHIN, SS CHEN, YY WEISS, LM AF MOMOSE, H JAFFE, ES SHIN, SS CHEN, YY WEISS, LM TI CHRONIC LYMPHOCYTIC-LEUKEMIA SMALL LYMPHOCYTIC LYMPHOMA WITH REED-STERNBERG LIKE CELLS AND POSSIBLE TRANSFORMATION TO HODGKINS-DISEASE - MEDIATION BY EPSTEIN-BARR-VIRUS SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE CHRONIC LYMPHOCYTIC LEUKEMIA; REED-STERNBERG CELLS; LEUKEMIA; EPSTEIN-BARR VIRUS ID RICHTERS SYNDROME; MYCOSIS-FUNGOIDES; EXPRESSION; TISSUES; GENE AB The pathogenesis of Reed-Sternberg cells and variants (RS-H cells) found in rare cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is unknown. We studied 13 such cases by immunohistochemistry and in situ hybridization for identification of Epstein-Barr virus (EBV) RNA. The RS-H cells in five cases expressed the B-lineage marker CD20 and were negative for CD15. In two cases, the RS-H cells showed expression of both CD20 and CD15, whereas in another six cases, the cells were positive for CD15 but negative for CD20. Three of the cases expressing CD15 showed subsequent evidence of disseminated Hodgkin's disease. Regardless of the phenotype or clinical behavior, the RS-H cells in 12 of 13 cases were found to contain EBV RNA by in situ hybridization, but the surrounding neoplastic lymphocytes were invariably negative for EBV RNA. It is suggested that EBV has an important role in the pathogenesis of the RS-H cells in these rare cases. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. RP MOMOSE, H (reprint author), CITY HOPE NATL MED CTR,DIV ANIM PATHOL,1500 E DUARTE RD,DUARTE,CA 91010, USA. FU NCI NIH HHS [CA 50341] NR 30 TC 111 Z9 112 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 1992 VL 16 IS 9 BP 859 EP 867 DI 10.1097/00000478-199209000-00004 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA JR437 UT WOS:A1992JR43700004 PM 1384376 ER PT J AU ZARATEOSORNO, A MEDEIROS, LJ LONGO, DL JAFFE, ES AF ZARATEOSORNO, A MEDEIROS, LJ LONGO, DL JAFFE, ES TI NON-HODGKINS-LYMPHOMAS ARISING IN PATIENTS SUCCESSFULLY TREATED FOR HODGKINS-DISEASE - A CLINICAL, HISTOLOGIC, AND IMMUNOPHENOTYPIC STUDY OF 14 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE HODGKINS DISEASE; NON-HODGKINS LYMPHOMA; B-CELL LINEAGE; IMMUNODEFICIENCY; MALIGNANT LYMPHOMA ID ACQUIRED IMMUNODEFICIENCY SYNDROME; REED-STERNBERG CELLS; LYMPHOPROLIFERATIVE DISORDERS; PARAFFIN SECTIONS; T-CELL; CANCER; ANTIBODIES; EXPRESSION; DIAGNOSIS; LEUKEMIA AB We report on 14 patients who developed Hodgkin's disease (HD), were successfully treated, and subsequently developed non-Hodgkin's lymphoma (NHL). The median interval between the diagnosis of HD and the diagnosis of NHL was 136 months (range 11-336). The clinical features of the patients with HD were similar to other patients with HD. Results of biopsies showed 12 nodular sclerosis and one mixed cellularity; one was not further classified. Immunophenotypic studies in nine cases showed that the Reed-Sternberg (RS) and Hodgkin's (H) cells were LeuM1+ LCA-. The patients were treated for HD in a nonuniform manner: two received radiation therapy, four received chemotherapy, and eight received both modalities. The NHLs were usually extranodal (79%) with frequent presentation as an abdominal mass. According to the Working Formulation, six lymphomas were small noncleaved cell (four non-Burkitt's, two Burkitt's), three were diffuse large cell, and two were follicular and diffuse large cell. Three neoplasms were not classified: two lymphomas with plasmacytoid differentiation were placed in the intermediate and low-grade categories, respectively, and one neoplasm was a plasmacytoma. All 14 neoplasms had an immunophenotype typical of NHL of B-cell lineage and were LeuM1-. Seven of the 12 patients treated with combination chemotherapy experienced a complete remission of their NHL. We conclude that the clinical, histologic, and immunophenotypic findings of the NHLs in these patients are analogous to those of NHLs that occur in immunosuppressed patients, suggesting that immunodeficiency plays a role in the pathogenesis of NHLs arising after HD. C1 NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,HEMATOPATHOL SECT,BLDG 10,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. NR 33 TC 43 Z9 44 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 1992 VL 16 IS 9 BP 885 EP 895 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA JR437 UT WOS:A1992JR43700007 PM 1415907 ER PT J AU LUFF, R KURMAN, R SOLOMON, D AF LUFF, R KURMAN, R SOLOMON, D TI THE BETHESDA SYSTEM FOR REPORTING CERVICAL VAGINAL CYTOLOGIC DIAGNOSES - REPORT OF THE 1991 BETHESDA WORKSHOP SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Editorial Material RP LUFF, R (reprint author), NCI,ROOM 2A19,BLDG 10,BETHESDA,MD 20892, USA. NR 5 TC 12 Z9 12 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 1992 VL 16 IS 9 BP 914 EP 916 PG 3 WC Pathology; Surgery SC Pathology; Surgery GA JR437 UT WOS:A1992JR43700011 ER PT J AU JACOBS, DR NELSON, ET DONTAS, AS KELLER, J SLATTERY, ML HIGGINS, M AF JACOBS, DR NELSON, ET DONTAS, AS KELLER, J SLATTERY, ML HIGGINS, M TI ARE RACE AND SEX-DIFFERENCES IN LUNG-FUNCTION EXPLAINED BY FRAME SIZE - THE CARDIA STUDY SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID FORCED EXPIRATORY VOLUME; PULMONARY-FUNCTION; VITAL CAPACITY; HEALTHY; NONSMOKERS; WHITE AB Using the CARDIA cohort of 20- to 32-yr-old black and white men and women, FVC and FEV1 were standardized for standing height, sitting height, leg height, elbow breadth, and biacromial diameter in such a way that the standardized lung function showed minimal statistical dependence on these measures of frame size. Race and sex differences in lung function have been reported even after adjustment for height; however, these differences might depend on aspects of frame size other than height. We found that within this age group height2 provided robust standardization for FVC and FEV1 for all race and sex strata of the population. Height explained approximately 40% of the variance of FVC and FEV1 in whites 30% in black women, and 20% In black men. In black men only, standardization for the combination of sitting height, leg height, elbow breadth, and biacromial diameter improved explained variance to nearly 40% for FVC and nearly 30% for FEV1. After standardization for height, FVC and FEV1 were found to be 14 to 19% higher in whites than in blacks, and in men than in women. Standardization of FVC and FEV1 for sitting height, leg height, elbow breadth, and biacromial diameter combined reduced these differences to 13-16%. Thus, race and sex differences in lung function exist even after detailed adjustment for frame size. C1 UNIV UTAH,SCH MED,SALT LAKE CITY,UT 84112. NHLBI,DEPT EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. CTR STUDIES AGE RELATED CHANGES MAN,ATHENS,GREECE. RP JACOBS, DR (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55454, USA. FU NHLBI NIH HHS [N01-HC-48048, N01-HC-48049, N01-HC-48047] NR 20 TC 32 Z9 33 U1 1 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD SEP PY 1992 VL 146 IS 3 BP 644 EP 649 PG 6 WC Respiratory System SC Respiratory System GA JM694 UT WOS:A1992JM69400019 PM 1519841 ER PT J AU COOPER, JD VREIM, CE AF COOPER, JD VREIM, CE TI BIOLOGY OF LUNG PRESERVATION FOR TRANSPLANTATION SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Editorial Material C1 NHLBI,DIV LUNG DIS,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892. NR 0 TC 59 Z9 60 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD SEP PY 1992 VL 146 IS 3 BP 803 EP 807 PG 5 WC Respiratory System SC Respiratory System GA JM694 UT WOS:A1992JM69400050 PM 1519869 ER PT J AU BUCHNER, J PASTAN, I BRINKMANN, U AF BUCHNER, J PASTAN, I BRINKMANN, U TI A METHOD FOR INCREASING THE YIELD OF PROPERLY FOLDED RECOMBINANT FUSION PROTEINS - SINGLE-CHAIN IMMUNOTOXINS FROM RENATURATION OF BACTERIAL INCLUSION-BODIES SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID PSEUDOMONAS EXOTOXIN; ESCHERICHIA-COLI; AERUGINOSA; REACTIVATION; EXPRESSION; CLONING; DOMAINS; GENES; MICE; B3 C1 NCI, DIV CANC BIOL DIAG & CTR, MOLEC BIOL LAB, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Buchner, Johannes/A-2651-2010 NR 21 TC 339 Z9 359 U1 3 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 EI 1096-0309 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP PY 1992 VL 205 IS 2 BP 263 EP 270 DI 10.1016/0003-2697(92)90433-8 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA JM682 UT WOS:A1992JM68200012 PM 1332541 ER PT J AU FURTH, PA SHAMAY, A WALL, RJ HENNIGHAUSEN, L AF FURTH, PA SHAMAY, A WALL, RJ HENNIGHAUSEN, L TI GENE-TRANSFER INTO SOMATIC TISSUES BY JET INJECTION SO ANALYTICAL BIOCHEMISTRY LA English DT Note ID TRANSGENIC MICE; EXPRESSION INVIVO; MAMMARY-GLAND; CELLS; PROMOTER; DNA; EXPLANTS; LIVER; VIRUS C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. USDA,INST LIVESTOCK & POULTRY SCI,GENE EVALUAT & MAPPING LAB,BELTSVILLE,MD 20705. RP FURTH, PA (reprint author), MAX PLANCK INST BIOPHYS CHEM,DEPT CELL BIOL,W-3400 GOTTINGEN,GERMANY. NR 22 TC 50 Z9 53 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP PY 1992 VL 205 IS 2 BP 365 EP 368 DI 10.1016/0003-2697(92)90449-H PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA JM682 UT WOS:A1992JM68200028 PM 1332543 ER PT J AU TODD, PJ SHORT, RT GRIMM, CC HOLLAND, WM MARKEY, SP AF TODD, PJ SHORT, RT GRIMM, CC HOLLAND, WM MARKEY, SP TI ORGANIC ION IMAGING USING TANDEM MASS-SPECTROMETRY SO ANALYTICAL CHEMISTRY LA English DT Article ID SURFACE-INDUCED DISSOCIATION; FAST ATOM BOMBARDMENT; BEAM PARAMETERS; LIQUID MATRICES; EMISSION; BIOMOLECULES; CHEMISTRY; GLYCEROL; SPECTRA AB A triple-quadrupole mass spectrometer has been interfaced with a wide-angle secondary ion microprobe. The combination permits acquisition of data necessary to determine the distribution of targeted organic analytes even in the presence of overwhelming isobaric interference. Micrographs generated from using secondary ion intensity alone are compared to those generated using secondary ionization with tandem mass spectrometry (MS/MS), both for image reference and to show the improvement in image quality that can be attained when MS/MS is employed. Inhomogeneous mixtures of glycerol, KCl, and asparagine on 1-cm-diameter aluminum targets were used to demonstrate the instrument's selectivity. Secondary ions generated from samples of this system Include isobaric Cs-133+ implanted from the primary ion beam, the g-41+-glycerol adduct, and protonated asparagine. C1 NIMH,BETHESDA,MD 20892. RP TODD, PJ (reprint author), OAK RIDGE NATL LAB,DIV ANALYT CHEM,BLDG 5510,POB 2008,OAK RIDGE,TN 37831, USA. FU NIGMS NIH HHS [R01 GM41617] NR 29 TC 13 Z9 13 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD SEP 1 PY 1992 VL 64 IS 17 BP 1871 EP 1878 DI 10.1021/ac00041a023 PG 8 WC Chemistry, Analytical SC Chemistry GA JK796 UT WOS:A1992JK79600024 PM 1416040 ER PT J AU STERN, DN SONG, MJ LANDIS, WJ AF STERN, DN SONG, MJ LANDIS, WJ TI TUBULE FORMATION AND ELEMENTAL DETECTION IN DEVELOPING OPOSSUM ENAMEL SO ANATOMICAL RECORD LA English DT Article ID ELECTRON-PROBE MICROANALYSIS; GROWTH PLATE CARTILAGE; RAT INCISOR; SECRETORY AMELOBLASTS; DIDELPHIS-MARSUPIALIS; MINERAL PHASE; PROTEOGLYCANS; ORGAN; CALCIUM; MICROSCOPY AB Most marsupials and some placental mammals possess enamel characterized by the presence of tubules, and the cellular origin of these structures has been the subject of a number of previous studies (See, for example, Lester, 1970; Azevedo and Goldberg, 1987). In the present report, tooth germs of the American opossum were examined to determine the structure and composition of enamel tubules during development and to analyze the enamel matrix relative to that of placental mammals with atubular enamel. For this purpose, tissues prepared by aqueous (decalcified and undecalcified) and anhydrous (undecalcified) methods were investigated by conventional transmission (TEM) and high voltage electron microscopy (HVEM), as well as by electron probe x-ray microanalysis (EPMA), selected-area electron diffraction (SAED), and electron spectroscopic imaging (ESI). Results indicate that most enamel tubules in the opossum begin as cytoplasmic remnants of Tomes' processes of ameloblasts. During development of the matrix, some of the tubules do not appear to be continuous throughout the prismatic layer. Sulfur is detectable around the lumen of the tubule in decalcified sections by EPMA and in and around the tubule by ESI. Calcium/phosphorus (Ca/P) molar ratios of the mineralizing matrix are generally higher than those found in enamel of other mammals and appear to decrease rather than increase with enamel maturation. The summary of data indicates the presence of sulfated glycoproteins or proteoglycans in this tissue, specifically around enamel tubules. Calcium and phosphorus are also present within the tubules, with the sulfated groups possibly binding calcium to prevent mineralization of the enamel tubules themselves. C1 HARVARD UNIV,DEPT BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,MARY INGRAHAM BUNTING INST,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT ORTHOPAED SURG,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,NIH BIOTECHNOL HVEM RESOURCE,ALBANY,NY 12201. RP STERN, DN (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIADDK NIH HHS [AM34078, AM34081]; NIDCR NIH HHS [DE07894] NR 83 TC 1 Z9 1 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD SEP PY 1992 VL 234 IS 1 BP 34 EP 48 DI 10.1002/ar.1092340105 PG 15 WC Anatomy & Morphology SC Anatomy & Morphology GA JH164 UT WOS:A1992JH16400004 PM 1329577 ER PT J AU GONZALEZ, FJ AF GONZALEZ, FJ TI INVITRO SYSTEMS FOR PREDICTION OF RATES OF DRUG CLEARANCE AND DRUG-INTERACTIONS SO ANESTHESIOLOGY LA English DT Editorial Material DE DRUG INTERACTIONS; PHARMACOGENETICS ID HUMAN LIVER; ALFENTANIL; CDNAS RP GONZALEZ, FJ (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA. NR 20 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1992 VL 77 IS 3 BP 413 EP 415 DI 10.1097/00000542-199209000-00001 PG 3 WC Anesthesiology SC Anesthesiology GA JL527 UT WOS:A1992JL52700001 PM 1519778 ER PT J AU ZWEIG, MH CSAKO, G AF ZWEIG, MH CSAKO, G TI NEW AUTOMATED NONISOTOPIC IMMUNOASSAYS FOR FREE-THYROXINE - EFFECT OF ALBUMIN AND THYROXINE-BINDING GLOBULIN CONCENTRATIONS SO ANNALS OF CLINICAL BIOCHEMISTRY LA English DT Article DE ONE-STEP ASSAY; 2-STEP ASSAY; INTERMETHOD CORRELATION; PRECISION ID SYSTEM AB Recently, nonisotopic (often automated) immunoassays for measuring serum free thyroxin (FT4) have become available. Though more costly than radioimmunoassays, they are considerably more convenient. We studied the influence of endogenous albumin and thyroxin-binding globulin concentration on five automated, nonisotopic methods of measuring FT4 [Enzymun on ES300 (one-step), Stratus I and II (essentially two-step), Delfia (two-step), and IM(x) (two-step)] in a mixed patient population. We observed that they (a) are influenced verv little by endogenous serum binding proteins and (b) seem to have sufficient within-run precision to justify performing single measurements on patients' specimens. RP ZWEIG, MH (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892, USA. NR 12 TC 4 Z9 4 U1 0 U2 0 PU ROYAL SOC MEDICINE SERVICES LTD PI LONDON PA 1 WIMPOLE STREET, LONDON, ENGLAND W1M 8AE SN 0004-5632 J9 ANN CLIN BIOCHEM JI Ann. Clin. Biochem. PD SEP PY 1992 VL 29 BP 551 EP 555 PN 5 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA JP650 UT WOS:A1992JP65000011 PM 1444168 ER PT J AU SPORN, MB ROBERTS, AB AF SPORN, MB ROBERTS, AB TI AUTOCRINE SECRETION - 10 YEARS LATER SO ANNALS OF INTERNAL MEDICINE LA English DT Review DE AUTOCRINE MOTILITY FACTOR; CYTOKINES; COLONY-STIMULATING FACTORS; INTERLEUKIN; TUMOR NECROSIS FACTOR; TRANSFORMING GROWTH FACTOR ID TRANSFORMING GROWTH-FACTOR; ACUTE PROMYELOCYTIC LEUKEMIA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; FACTOR-BETA-1 GENE-EXPRESSION; TRANS RETINOIC ACID; FACTOR-BETA; CELL-SURFACE; FACTOR-ALPHA; RECEPTOR SUPERFAMILY AB The concept of autocrine secretion, its subsequent modifications, its application for understanding pathogenesis of disease, and its potential for developing new approaches to prevention and treatment are reviewed. Peptide growth factors (cytokines) act as local autocrine and paracrine mediators of tissue homeostasis. Many diseases, including cancer, atherosclerosis, rheumatoid arthritis, and other fibrotic diseases characterized by chronic inflammation, are associated with aberrant expression and cellular coordination of the homeostatic action of these regulatory molecules. Modern biotechnology and pharmacology offer unique opportunities for the therapeutic prevention and treatment of these molecular and cellular lesions, using either cytokines or other agents that modify their synthesis and activity. RP SPORN, MB (reprint author), NCI, BLDG 41, ROOM C629, BETHESDA, MD 20892 USA. NR 90 TC 140 Z9 140 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 1992 VL 117 IS 5 BP 408 EP 414 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA JK678 UT WOS:A1992JK67800011 PM 1503333 ER PT J AU SHELHAMER, JH TOEWS, GB MASUR, H SUFFREDINI, AF PIZZO, PA WALSH, TJ HENDERSON, DK AF SHELHAMER, JH TOEWS, GB MASUR, H SUFFREDINI, AF PIZZO, PA WALSH, TJ HENDERSON, DK TI RESPIRATORY-DISEASE IN THE IMMUNOSUPPRESSED PATIENT SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE IMMUNOSUPPRESSION; RESPIRATORY TRACT DISEASES; RESPIRATORY INSUFFICIENCY; COLONY-STIMULATING FACTORS; IMMUNIZATION; ACQUIRED IMMUNODEFICIENCY SYNDROME; HUMAN IMMUNODEFICIENCY VIRUS ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED IMMUNODEFICIENCY SYNDROME; COLONY-STIMULATING FACTOR; PLACEBO-CONTROLLED TRIAL; NEUTROPHIL CHEMOTACTIC FACTOR; ACUTE NONLYMPHOCYTIC LEUKEMIA; CYTOMEGALO-VIRUS INFECTION; PLUS AMPHOTERICIN-B; OPEN LUNG-BIOPSY; BRONCHOALVEOLAR LAVAGE AB Pulmonary complications, both infectious and noninfectious, are an important cause of morbidity in patients with various types of immunosuppression. The appropriate response to these clinical problems requires an understanding of pulmonary host defense and of the various types of systemic immunosuppression. Infectious and noninfectious pulmonary complications may vary according to the type of immunosuppression as well as to the degree and duration of immunosuppression. Appropriate clinical management also requires an understanding of the clinical problems commonly seen in specific groups of immunosuppressed patients and an understanding of the sensitivity, specificity, and potential complications associated with the available diagnostic approaches to those patients. Because respiratory disease in these patient groups may progress rapidly to respiratory failure, an expeditious evaluation based on the knowledge of likely causes of respiratory disease and prompt specific or empiric therapy are indicated. Specific sets of algorithms for the evaluation of both focal and diffuse pulmonary disease may facilitate such an evaluation. In addition, an aggressive approach to the prevention of pulmonary disease including immunization, prophylaxis, and immunomodulation (for example, colony stimulating factors) may be warranted in specific subgroups at risk. RP SHELHAMER, JH (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 101 TC 50 Z9 52 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 1992 VL 117 IS 5 BP 415 EP 431 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA JK678 UT WOS:A1992JK67800012 PM 1503334 ER PT J AU LENFANT, C AF LENFANT, C TI STRATEGIES FOR ELECTIVE RED-BLOOD-CELL TRANSFUSION SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 1992 VL 117 IS 5 BP 441 EP 441 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JK678 UT WOS:A1992JK67800017 PM 1463539 ER PT J AU DAWSON, TM DAWSON, VL SNYDER, SH AF DAWSON, TM DAWSON, VL SNYDER, SH TI A NOVEL NEURONAL MESSENGER MOLECULE IN BRAIN - THE FREE-RADICAL, NITRIC-OXIDE SO ANNALS OF NEUROLOGY LA English DT Article ID SOLUBLE GUANYLATE-CYCLASE; LONG-TERM POTENTIATION; VASOACTIVE INTESTINAL POLYPEPTIDE; DEPENDENT PROTEIN-KINASE; CYCLIC-GMP LEVELS; SELECTIVE METABOLIC INHIBITION; NMDA RECEPTOR ACTIVATION; RAT ANOCOCCYGEUS MUSCLE; NG-MONOMETHYL ARGININE; CENTRAL NERVOUS-SYSTEM AB Understanding of the organization and function of a newly identified neuronal messenger molecule, nitric oxide, has progressed rapidly. Nitric oxide synthase has been purified and molecularly cloned from brain. Its localization is exclusively neuronal and endothelial. The catalytic activity of nitric oxide synthase accounts for the NADPH diaphorase staining of neurons that are uniquely resistant to toxic insults and neurodegenerative disorders. Nitric oxide has diverse functions. In platelets it inhibits their aggregation, in macrophages it mediates cytotoxicity, and in blood vessels it acts as a vasodilator. In the nervous system nitric oxide may be the retrograde transmitter in long-term potentiation. It is the "neurotransmitter" of cerebral vasodilator nerves and the inhibitory "neurotransmitter" of the motor neurons of the intestines. Nitric oxide in situations of excessive production may function as a neurotoxin, suggesting a role for nitric oxide in neurodegenerative disorders. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,725 N WOLFE ST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. NATL INST DRUG ABUSE,ADDICTION RES CTR,MOLEC NEUROBIOL,BALTIMORE,MD. OI Dawson, Valina/0000-0002-2915-3970 FU NIDA NIH HHS [DA 271-90-7408, DA-00266]; NIMH NIH HHS [MH-18501] NR 187 TC 766 Z9 781 U1 0 U2 11 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1992 VL 32 IS 3 BP 297 EP 311 DI 10.1002/ana.410320302 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JN145 UT WOS:A1992JN14500001 PM 1384420 ER PT J AU PFALLER, MA DUPONT, B KOBAYASHI, GS MULLER, J RINALDI, MG ESPINELINGROFF, A SHADOMY, S TROKE, PF WALSH, TJ WARNOCK, DW AF PFALLER, MA DUPONT, B KOBAYASHI, GS MULLER, J RINALDI, MG ESPINELINGROFF, A SHADOMY, S TROKE, PF WALSH, TJ WARNOCK, DW TI STANDARDIZED SUSCEPTIBILITY TESTING OF FLUCONAZOLE - AN INTERNATIONAL COLLABORATIVE STUDY SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIFUNGAL AGENTS; FUNGAL-INFECTIONS; AMPHOTERICIN-B; TRIAZOLES; IMIDAZOLE; INVITRO AB An international collaborative study of broth dilution (MIC) and disk diffusion susceptibility testing of fluconazole was conducted by using a chemically defined medium (High-Resolution Antifungal Assay Medium; Oxoid Ltd., Basingstoke, United Kingdom) and standard test methods performed in eight reference laboratories. Ten yeast isolates were tested by each test method in duplicate on each of 3 separate days. The intralaboratory reproducibility of the MIC test was excellent; 95.7% of the replicate tests (n = 220) were within 2 doubling dilutions of the other values in the set for the eight laboratories. The intralaboratory reproducibility of the disk test was also good, with 91% of the replicate tests (n = 234) agreeing with each other within an arbitrarily chosen value of 4 mm. Interlaboratory agreement of MIC test results was acceptable, with 84% of the MICs agreeing within 2 doubling dilutions. In contrast, the interlaboratory agreement of the disk test was not good, with only 59% of test results agreeing within 4 mm. Comparison of the rank order of MICs obtained in each laboratory with the reference rank order gave an agreement of 70 to 80% (median, 80%) with the MIC test and 70 to 90% (median, 80%) with the disk test. These preliminary results are encouraging for the development of standardized testing methods for testing fluconazole. C1 WASHINGTON UNIV,SCH MED,DIV LAB MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. DEPT VET AFFAIRS MED CTR,SAN ANTONIO,TX. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MED,RICHMOND,VA 23298. BRISTOL ROYAL INFIRM & GEN HOSP,DEPT MICROBIOL,REG MYCOL LAB,BRISTOL BS2 8HW,AVON,ENGLAND. HOSP INST PASTEUR,F-75015 PARIS,FRANCE. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. UNIV FREIBURG,INST MED MICROBIOL & HYG,MYCOL SECT,W-7800 FREIBURG,GERMANY. PFIZER LTD,SANDWICH,ENGLAND. NCI,BETHESDA,MD 20892. RP PFALLER, MA (reprint author), OREGON HLTH SCI UNIV,DEPT PATHOL,PORTLAND,OR 97201, USA. NR 30 TC 74 Z9 75 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 1992 VL 36 IS 9 BP 1805 EP 1809 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA JM247 UT WOS:A1992JM24700002 PM 1416871 ER PT J AU WALZER, PD FOY, J STEELE, P KIM, CK WHITE, M KLEIN, RS OTTER, BA ALLEGRA, C AF WALZER, PD FOY, J STEELE, P KIM, CK WHITE, M KLEIN, RS OTTER, BA ALLEGRA, C TI ACTIVITIES OF ANTIFOLATE, ANTIVIRAL, AND OTHER DRUGS IN AN IMMUNOSUPPRESSED RAT MODEL OF PNEUMOCYSTIS-CARINII PNEUMONIA SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AIDS-RELATED COMPLEX; TRIMETHOPRIM-SULFAMETHOXAZOLE; DIHYDROPTEROATE SYNTHASE; DIHYDROFOLATE-REDUCTASE; ANTIMICROBIAL AGENTS; CONTROLLED TRIAL; THERAPY; EFFICACY; PENTAMIDINE AB The efficacy of antifolate, antiviral, and other drugs was compared in an experimental model of pneumocystosis. Sulfamethoxazole (SMX) administered alone in doses of greater-than-or-equal-to 60 mg/kg/day was highly effective in treatment and prophylaxis. Low (less-than-or-equal-to 15 mg/kg/day) doses of SMX showed limited, dose-related anti-Pneumocystis carinii activity in therapy but were more effective in prophylaxis. The dihydrofolate reductase (DHFR) inhibitors trimethoprim (TMP), pyrimethamine, and trimetrexate exhibited little anti-P. carinii activity when administered alone and did not enhance the efficacy of SMX; the effects of the DHFR inhibitors could not be related to the dose or the concentration in serum. These data suggested that the rat model is an excellent system for studying the anti-P. carinii activity of sulfonamides but is of limited value in studying DHFR inhibitors. The antiviral drugs azidothymidine, dideoxyinosine, inosine pranobex (Isoprinosine), amantadine, and acyclovir displayed little or no activity against P. carinii; however, azidothymidine did not impair the efficacy of SMX or TMP-SMX. These results supported the clinical practice of giving antiviral agents together with antifolate drugs to patients infected with human immunodeficiency virus and suggested that the beneficial effects of antiviral agents on the occurrence of pneumocystosis are due mainly to their effects on the virus or the host immune response. In contrast to the antiviral drugs, 9-deazainosine, a nucleoside analog with antiprotozoal properties, demonstrated marked activity against P. carinii which was related to dose and route of administration. These data raised the possibility that anti-P. carinii activity is a general property of purine nucleosides and suggested that further exploration of this class of compounds might lead to clinically useful agents. C1 UNIV CINCINNATI,SCH MED,DEPT INTERNAL MED,DIV INFECT DIS,CINCINNATI,OH 45221. UNIV CINCINNATI,SCH MED,DEPT ENVIRONM HLTH,DIV BIOSTAT,CINCINNATI,OH 45221. MONTEFIORE MED CTR,DEPT ONCOL,BRONX,NY 10467. NCI,MED BRANCH,BETHESDA,MD 20892. RP WALZER, PD (reprint author), VET ADM MED CTR,DEPT INTERNAL MED,DIV INFECT DIS,CINCINNATI,OH 45220, USA. FU NHLBI NIH HHS [HL 46653]; NIAID NIH HHS [AI 25897, N01-AI-72646] NR 41 TC 61 Z9 61 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 1992 VL 36 IS 9 BP 1935 EP 1942 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA JM247 UT WOS:A1992JM24700024 PM 1416884 ER PT J AU HIRAMATSU, Y HORN, VJ BAUM, BJ AMBUDKAR, IS AF HIRAMATSU, Y HORN, VJ BAUM, BJ AMBUDKAR, IS TI CHARACTERIZATION OF POLYPHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE-C IN RAT PAROTID-GLAND MEMBRANES SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE HYDROLYSIS; GUANINE-NUCLEOTIDE; ACINAR-CELLS; GUANOSINE 5'-O-(3-THIOTRIPHOSPHATE); ALPHA-SUBUNITS; CALCIUM ENTRY; SUBSTANCE-P; ACTIVATION; RECEPTOR; PROTEINS C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892. NR 36 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP PY 1992 VL 297 IS 2 BP 368 EP 376 DI 10.1016/0003-9861(92)90686-Q PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JH366 UT WOS:A1992JH36600026 PM 1323243 ER PT J AU SWEDO, SE PIETRINI, P LEONARD, HL SCHAPIRO, MB RETTEW, DC GOLDBERGER, EL RAPOPORT, SI RAPOPORT, JL GRADY, CL AF SWEDO, SE PIETRINI, P LEONARD, HL SCHAPIRO, MB RETTEW, DC GOLDBERGER, EL RAPOPORT, SI RAPOPORT, JL GRADY, CL TI CEREBRAL GLUCOSE-METABOLISM IN CHILDHOOD-ONSET OBSESSIVE-COMPULSIVE DISORDER - REVISUALIZATION DURING PHARMACOTHERAPY SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; TRANSMISSION MEASUREMENTS; RATES; CLOMIPRAMINE AB To investigate the effects of drug treatment in childhood-onset obsessive-compulsive disorder (OCD), we repeated positron emission tomographic scans in 13 adults with OCD (eight taking clomipramine, two taking fluoxetine, and three taking no drug) after at least 1 year of pharmacotherapy. As a group, the patients had a significant improvement on all OCD and anxiety ratings. Positron emission tomography revealed a significant decrease in normalized orbitofrontal regional cerebral glucose metabolism (relative to global metabolism) bilaterally. Among the treated patients, the decrease in right orbitofrontal metabolism was directly correlated with two measures of OCD improvement These results extend previous positron emission tomographic findings of regional dysfunction in OCD and suggest involvement of the orbitofrontal regions in the pathophysiology of OCD. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. RP SWEDO, SE (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 27 TC 321 Z9 321 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 1992 VL 49 IS 9 BP 690 EP 694 PG 5 WC Psychiatry SC Psychiatry GA JM052 UT WOS:A1992JM05200002 PM 1514873 ER PT J AU SMITH, SS OHARA, BF PERSICO, AM GORELICK, DA NEWLIN, DB VLAHOV, D SOLOMON, L PICKENS, R UHL, GR AF SMITH, SS OHARA, BF PERSICO, AM GORELICK, DA NEWLIN, DB VLAHOV, D SOLOMON, L PICKENS, R UHL, GR TI GENETIC VULNERABILITY TO DRUG-ABUSE - THE D2 DOPAMINE RECEPTOR TAQ I B1 RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM APPEARS MORE FREQUENTLY IN POLYSUBSTANCE ABUSERS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT MEETING ON D-2 RECEPTOR ALLELES IN SUBSTANCE ABUSE : HAVE WE IDENTIFIED A RELEVANT GENE CY SEP 19, 1991 CL BALTIMORE, MD ID ALCOHOLISM; ASSOCIATION; HETEROGENEITY; INHERITANCE; POPULATION; ALLELE; LOCUS AB Alcoholics are more likely than nonalcoholics to display the Taq I A1 restriction fragment length polymorphism of the D2 dopamine receptor gene, according to four of six studies that examined alcoholics and controls. The current study examines whether the association observed in alcoholism might extend to other addictive substances by examining D2 dopamine receptor Taq I A and B restriction fragment length polymorphisms in polysubstance users and controls free of significant substance use. We hypothesized a stronger association for the B1 restriction fragment length polymorphism since it lies closer to dopamine receptor protein coding and 5' regulatory regions. Heavy polysubstance users and subjects with DSM-III-R psychoactive substance use diagnoses displayed significantly higher Taq I B1 frequencies than control subjects, Taq I A1 results for these comparisons were less robust. These results are consistent with a role for a D2 dopamine receptor gene variant marked by these restriction fragment length polymorphisms in enhanced substance abuse vulnerability. C1 NIDA,ADDICT RES CTR,BETHESDA,MD. UNIV MARYLAND,DEPT PSYCHIAT,COLL PK,MD 20742. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. NR 38 TC 169 Z9 172 U1 4 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 1992 VL 49 IS 9 BP 723 EP 727 PG 5 WC Psychiatry SC Psychiatry GA JM052 UT WOS:A1992JM05200008 PM 1355337 ER PT J AU INSEL, TR AF INSEL, TR TI TOWARD A NEUROANATOMY OF OBSESSIVE-COMPULSIVE DISORDER SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Note ID GLUCOSE METABOLIC RATES; CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; BASAL GANGLIA; MAGNETIC-RESONANCE; LESIONS; CORTEX; ABNORMALITIES; ORGANIZATION; INTERFERENCE RP INSEL, TR (reprint author), NIMH,NEUROPHYSIOL LAB,POB 289,POOLESVILLE,MD 20837, USA. NR 57 TC 364 Z9 369 U1 4 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 1992 VL 49 IS 9 BP 739 EP 744 PG 6 WC Psychiatry SC Psychiatry GA JM052 UT WOS:A1992JM05200010 PM 1514879 ER PT J AU WELLER, M KORNHUBER, J AF WELLER, M KORNHUBER, J TI N-METHYL-D-ASPARTATE ANTAGONISTS, SCHIZOPHRENIA, AND NEUROLEPTIC MALIGNANT SYNDROME SO ARCHIVES OF NEUROLOGY LA English DT Letter ID POSTMORTEM BRAIN; ACID C1 UNIV WURZBURG,DEPT PSYCHIAT,W-8700 WURZBURG,GERMANY. RP WELLER, M (reprint author), NIH,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 3N256,BETHESDA,MD 20892, USA. RI Kornhuber, Johannes/B-9613-2014 OI Kornhuber, Johannes/0000-0002-8096-3987 NR 10 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 1992 VL 49 IS 9 BP 900 EP 901 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA JM337 UT WOS:A1992JM33700002 PM 1472253 ER PT J AU TAKAHASHI, Y WYMAN, M FERRIS, F KADOR, PF AF TAKAHASHI, Y WYMAN, M FERRIS, F KADOR, PF TI DIABETES-LIKE PREPROLIFERATIVE RETINAL CHANGES IN GALACTOSE-FED DOGS SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID ALDOSE REDUCTASE LOCALIZATION; DIABETIC-LIKE RETINOPATHY; ENDOTHELIAL-CELLS; MURAL CELLS; PERICYTES; COMPLICATIONS; CAPILLARIES; PROGRESSION; PREVENTION; INHIBITORS AB Retinal vessel changes were experimentally investigated by a combination of color fundus photography, fluorescein angiography, and histologic studies in beagles that were fed a 30% galactose diet for up to 66 months. Previously, we have described the appearance of pericyte ghosts, microaneurysms, acellular capillaries, and intraretinal hemorrhages in dogs fed a galactose diet for up to 36 months. These disorders were similar to those observed in humans with background diabetic retinopathy. We report herein that dogs fed galactose for 48 to 60 months experience retinal changes associated with the chronic occlusion of capillary beds and subsequent ischemia of the retina. These changes included the appearance of broad areas of nonperfusion, soft exudates (cytoid bodies), intraretinal microvascular abnormalities, occluded arterioles, preretinal and intravitreal hemorrhages, and apparent new vessel growth around the optic disc. The present study clearly demonstrates that the galactose-fed dog is an animal model in which advanced retinal changes develop, and these changes are similar to those associated with preproliferative human diabetic retinopathy. C1 NEI,BLDG 10,ROOM 10B11,BETHESDA,MD 20892. OHIO STATE UNIV,COLL VET MED,COLUMBUS,OH 43210. NR 28 TC 47 Z9 47 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1992 VL 110 IS 9 BP 1295 EP 1302 PG 8 WC Ophthalmology SC Ophthalmology GA JL634 UT WOS:A1992JL63400030 PM 1520120 ER PT J AU ZARATEOSORNO, A MEDEIROS, LJ JAFFE, ES AF ZARATEOSORNO, A MEDEIROS, LJ JAFFE, ES TI HODGKINS-DISEASE COEXISTENT WITH PLASMA-CELL DYSCRASIA SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Note ID IMMUNOGLOBULIN GENE REARRANGEMENTS; CASTLEMANS DISEASE; LYMPHOMA AB We describe a case of Hodgkin's disease, mixed cellularity type, associated with nodal monotypic plasma cells and monoclonal serum gammopathy. Although plasma cells are often found in tissues involved by Hodgkin's disease and may be numerous, the occurrence of Hodgkin's disease with monotypic plasmacytosis and/or monoclonal serum gammopathy is rare. The simultaneous occurrence of Hodgkin's disease and monotypic plasma cell proliferation may represent a coincidental occurrence. However, previously we have described cases of Hodgkin's disease associated with B-cell non-Hodgkin's lymphoma, perhaps suggesting a relationship between the Reed-Sternberg and Hodgkin cells and B-lineage lymphoid cells. The case presented further extends these observations. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BLDG 10,ROOM 2N202,BETHESDA,MD 20892. NR 20 TC 6 Z9 6 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 1992 VL 116 IS 9 BP 969 EP 972 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA JL756 UT WOS:A1992JL75600022 PM 1524465 ER PT J AU SILVER, RM MCKINLEY, K SMITH, EA QUEARRY, B HARATI, Y STERNBERG, EM HEYES, MP AF SILVER, RM MCKINLEY, K SMITH, EA QUEARRY, B HARATI, Y STERNBERG, EM HEYES, MP TI TRYPTOPHAN-METABOLISM VIA THE KYNURENINE PATHWAY IN PATIENTS WITH THE EOSINOPHILIA-MYALGIA-SYNDROME SO ARTHRITIS AND RHEUMATISM LA English DT Article ID QUINOLINIC ACID CONCENTRATIONS; SCLERODERMA-LIKE ILLNESS; INDOLEAMINE 2,3-DIOXYGENASE; INTERFERON-GAMMA; CEREBROSPINAL-FLUID; CLINICAL SPECTRUM; HUMAN-FIBROBLASTS; RAT-BRAIN; PEAK-E; INDUCTION AB Objective. To investigate the metabolism of L-tryptophan (LT) via the kynureni Methods. Measurement of LT, L-kynurenine, and quinolinic acid in plasma and cerebrospinal fluid (CSF) from subjects with EMS, from asymptomatic users of LT, and from normal subjects. Results. Plasma LT concentrations were lower in untreated EMS patients (n = 5) than in corticosteroid-treated EMS patients (n = 5; P < 0.05) and in asymptomatic users of LT (n = 5; P < 0.05). Untreated EMS patients, who had discontinued LT weeks to months prior to study, had significantly higher plasma levels of L-kynurenine and quinolinic acid than did corticosteroid-treated EMS patients (P < 0.05), normal subjects (P < 0.02), and asymptomatic users of LT (P < 0.05). EMS patients also had significantly elevated levels of L-kynurenine (P < 0.05) and quinolinic acid (P < 0.001) in CSF compared with normal subjects. After a 1-gm oral dose of LT, untreated EMS patients (n = 4) showed lower peak levels of LT and accentuated synthesis of L-kynurenine and quinolinic acid, compared with these values in corticosteroid-treated EMS patients (n 2), who responded like normal subjects (n = 5). Conclusion. These data demonstrate that during the active phase of EMS, LT metabolism via the kynurenine pathway was accentuated, probably secondary to induction of the enzyme indoleamine-2,3-dioxygenase. Ingestion of large amounts of LT (median daily dose 1.5 gm) resulted in high concentrations of kynurenine-pathway metabolites in blood and extrahepatic tissues, which was accentuated in EMS patients and which may have played a significant role in the pathogenesis of the disease. C1 BAYLOR COLL MED, DEPT NEUROL, HOUSTON, TX 77030 USA. NIMH, BETHESDA, MD 20892 USA. NIAID, BETHESDA, MD 20892 USA. RP MED UNIV S CAROLINA, DEPT MED, 912 CLIN SCI BLDG, 171 ASHLEY AVE, CHARLESTON, SC 29425 USA. FU NCRR NIH HHS [RR 01070-13] NR 41 TC 34 Z9 34 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 BP 1097 EP 1105 DI 10.1002/art.1780350916 PG 9 WC Rheumatology SC Rheumatology GA JQ530 UT WOS:A1992JQ53000015 PM 1418026 ER PT J AU BATHON, J HWANG, J SHIN, L PRECHT, P HORTON, W AF BATHON, J HWANG, J SHIN, L PRECHT, P HORTON, W TI TYPE-VI COLLAGEN SPECIFIC MESSENGER-RNA IS EXPRESSED CONSTITUTIVELY BY HUMAN SYNOVIAL FIBROBLASTS (HSF) AND IS DOWN-REGULATED BY INTERLEUKIN-1 (IL-1) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S192 EP S192 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800929 ER PT J AU BERMAS, BL SHEARER, GM MOZES, E AF BERMAS, BL SHEARER, GM MOZES, E TI DIFFERENT KINETICS OF INTERLEUKIN-2 AND INTERLEUKIN-4 PRODUCTION FOLLOWING INDUCTION OF EXPERIMENTAL SYSTEMIC LUPUS-ERYTHEMATOSUS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. WEIZMANN INST SCI,IL-76100 REHOVOT,ISRAEL. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S206 EP S206 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15801015 ER PT J AU BERMAS, BL PETRI, M BERZOFSKY, JA SHEARER, GN MOZES, E AF BERMAS, BL PETRI, M BERZOFSKY, JA SHEARER, GN MOZES, E TI AUTOANTIBODIES SPECIFIC TO GP120 AND HIV-1 ENVELOPE PEPTIDES IN SLE PATIENTS AND IN MICE WITH EXPERIMENTAL SLE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NCI,EI B,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. WEIZMANN INST SCI,IL-76100 REHOVOT,ISRAEL. JOHNS HOPKINS UNIV,MED CTR,BALTIMORE,MD 21218. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S168 EP S168 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800785 ER PT J AU BERMAS, BL PETRI, M GOLDMAN, D STOCK, NI MILLER, MW VIA, CS SHEARER, GM AF BERMAS, BL PETRI, M GOLDMAN, D STOCK, NI MILLER, MW VIA, CS SHEARER, GM TI PROGRESSIVE IMPAIRMENT OF LYMPHOCYTE-T FUNCTION IS CORRELATED WITH DISEASE-ACTIVITY IN A COHORT OF SLE OUTPATIENTS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,MED CTR,BALTIMORE,MD 21218. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S159 EP S159 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800738 ER PT J AU BOUMPAS, DT AUSTIN, HA VAUGHAN, E KLIPPEL, JH STEINBERG, AD YARBORO, CH BALOW, JE AF BOUMPAS, DT AUSTIN, HA VAUGHAN, E KLIPPEL, JH STEINBERG, AD YARBORO, CH BALOW, JE TI A RANDOMIZED STUDY OF 2 REGIMENS OF PULSE CYCLOPHOSPHAMIDE (CY) VERSUS PULSE METHYLPREDNISOLONE (MP) IN SEVERE LUPUS NEPHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S54 EP S54 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800116 ER PT J AU BOUMPAS, DT AUSTIN, HA VAUGHAN, EM YARBORO, CH KLIPPEL, JH BALOW, JE AF BOUMPAS, DT AUSTIN, HA VAUGHAN, EM YARBORO, CH KLIPPEL, JH BALOW, JE TI RISK OF AMENORRHEA IN LUPUS PATIENTS TREATED WITH PULSE CYCLOPHOSPHAMIDE THERAPY SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S54 EP S54 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800118 ER PT J AU CHIKANZA, IC PETROU, P KINGSLEY, G CHROUSOS, G PANAYI, GS AF CHIKANZA, IC PETROU, P KINGSLEY, G CHROUSOS, G PANAYI, GS TI DEFECTIVE PROLACTIN (PL) AND CORTISOL (CS) RESPONSE TO SURGERY IN RHEUMATOID-ARTHRITIS (RA) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 GUYS HOSP,RHEUMATOL UNIT,LONDON SE1 9RT,ENGLAND. ORSAGOS REUMA,BUDAPEST,HUNGARY. NICHHD,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S197 EP S197 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800961 ER PT J AU CROFFORD, LJ SANO, H KARALIS, K FRIEDMAN, TC REMMERS, EF CHROUSOS, GP WILDER, RL AF CROFFORD, LJ SANO, H KARALIS, K FRIEDMAN, TC REMMERS, EF CHROUSOS, GP WILDER, RL TI CHARACTERIZATION OF CORTICOTROPIN-RELEASING HORMONE LOCALIZED IN SYNOVIAL TISSUES AND FLUIDS OF PATIENTS WITH RHEUMATOID-ARTHRITIS AND OSTEOARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Crofford, Leslie/J-8010-2013 NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S146 EP S146 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800659 ER PT J AU CROFFORD, LJ SANO, H KARALIS, K WEBSTER, EL GOLDMUNTZ, EA CHROUSOS, GP WILDER, RL AF CROFFORD, LJ SANO, H KARALIS, K WEBSTER, EL GOLDMUNTZ, EA CHROUSOS, GP WILDER, RL TI LOCAL SECRETION OF CORTICOTROPIN-RELEASING HORMONE IN THE JOINTS OF LEWIS RATS WITH INFLAMMATORY ARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S98 EP S98 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800374 ER PT J AU DAWISHA, SM YARBORO, C AUSTIN, HA BALOW, JE KLIPPEL, JH AF DAWISHA, SM YARBORO, C AUSTIN, HA BALOW, JE KLIPPEL, JH TI MONTHLY ORAL BOLUS CYCLOPHOSPHAMIDE THERAPY IN SYSTEMIC LUPUS-ERYTHEMATOSUS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD. NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S153 EP S153 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800698 ER PT J AU DELPUENTE, A HEVSE, S MANTOVA, D MANDES, MG SCARPA, R ORIENTE, P AF DELPUENTE, A HEVSE, S MANTOVA, D MANDES, MG SCARPA, R ORIENTE, P TI LOW INCIDENCE OF HIP FRACTURE OBSERVED ON THE ISLAND-OF-ISCHIA (ITALY) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MED SCH NAPLES,RHEUMATOL UNIT 2,I-80131 NAPLES,ITALY. NIAMSK,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S178 EP S178 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800848 ER PT J AU GOURLEY, M SCOTT, D MUIR, J BALOW, J AUSTIN, H STEINBERG, A AF GOURLEY, M SCOTT, D MUIR, J BALOW, J AUSTIN, H STEINBERG, A TI RANDOMIZED TRIAL OF MONTHLY METHYLPREDNISOLONE (MP) VERSUS CYCLOPHOSPHAMIDE (CY) OR BOTH IN LUPUS NEPHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S56 EP S56 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800127 ER PT J AU HOCHBERG, MC LETHBRIDGECEIKU, M SCOTT, WW PLATO, CC TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEIKU, M SCOTT, WW PLATO, CC TOBIN, JD TI DECREASED SERUM LEVELS OF INSULIN-LIKE GROWTH FACTOR-I IN WOMEN WITH OSTEOARTHRITIS OF THE HAND - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING (BLSA) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S93 EP S93 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800342 ER PT J AU HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW PLATO, C TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW PLATO, C TOBIN, JD TI THE ASSOCIATION OF OBESITY AND FAT DISTRIBUTION WITH OSTEOARTHRITIS OF THE HANDS IN WOMEN - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S82 EP S82 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800278 ER PT J AU HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW PLATO, CC TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW PLATO, CC TOBIN, JD TI THE RELATIONSHIP BETWEEN BONE MASS AND OSTEOARTHRITIS OF THE HANDS IN WOMEN - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S82 EP S82 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800277 ER PT J AU HOFFMAN, GS LEAVITT, RY KERR, GS FAUCI, AS AF HOFFMAN, GS LEAVITT, RY KERR, GS FAUCI, AS TI THE TREATMENT OF WEGENERS GRANULOMATOSIS (WG) WITH GLUCOCORTICOIDS (GC) AND METHOTREXATE (MTX) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S52 EP S52 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800103 ER PT J AU JACOBSSON, LTH KNOWLER, WC PILLEMER, SR HANSON, RL PETTITT, DJ NELSON, RG MCCANCE, DR CHARLES, MA BENNETT, PH AF JACOBSSON, LTH KNOWLER, WC PILLEMER, SR HANSON, RL PETTITT, DJ NELSON, RG MCCANCE, DR CHARLES, MA BENNETT, PH TI MORTALITY AND RHEUMATOID-ARTHRITIS - A LONGITUDINAL POPULATION-BASED STUDY IN PIMA-INDIANS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,PHOENIX,AZ 85014. NIDDK,PHOENIX,AZ 85014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S47 EP S47 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800077 ER PT J AU KATZ, P WHALEN, G KEHRL, JH AF KATZ, P WHALEN, G KEHRL, JH TI DIFFERENTIAL EXPRESSION OF A NOVEL PROTEIN-KINASE IN GERMINAL CENTER VERSUS NONGERMINAL CENTER LYMPHOCYTES-B SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 GEORGETOWN UNIV,WASHINGTON,DC 20057. NIAID,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S61 EP S61 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800160 ER PT J AU KERR, GS FLEISHER, TA HALLAHAN, CW LEAVITT, RY FAUCI, AS HOFFMAN, GS AF KERR, GS FLEISHER, TA HALLAHAN, CW LEAVITT, RY FAUCI, AS HOFFMAN, GS TI LIMITED PROGNOSTIC VALUE OF THE ANTINEUTROPHIL CYTOPLASMIC ANTIBODY (C-ANCA) IN PATIENTS WITH WEGENERS GRANULOMATOSIS (WG) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S115 EP S115 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800474 ER PT J AU LEFF, RL BUCZEK, FL HICKS, J GERBER, L AF LEFF, RL BUCZEK, FL HICKS, J GERBER, L TI A STUDY OF FALLING - SLIPS AND TRIPS IN A PATIENT WITH MUSCLE WEAKNESS DUE TO MYOSITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S291 EP S291 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15801293 ER PT J AU LEFF, RL NICASTRI, CG NICHOLS, RC RABEN, N PLOTZ, PH KLINMAN, D AF LEFF, RL NICASTRI, CG NICHOLS, RC RABEN, N PLOTZ, PH KLINMAN, D TI IDENTIFICATION AND QUANTITATION OF INDIVIDUAL B-CELLS SECRETING ANTI-JO-1 ANTIBODIES IN PATIENTS WITH MYOSITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S71 EP S71 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800215 ER PT J AU LETHBRIDGECEJKU, M TOBIN, JD PLATO, CC HOCHBERG, MC AF LETHBRIDGECEJKU, M TOBIN, JD PLATO, CC HOCHBERG, MC TI VALIDITY OF 2 NEW METHODS FOR ASSESSING PROGRESSION OF RADIOGRAPHIC CHANGES OF HAND OSTEOARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S82 EP S82 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800281 ER PT J AU LOVE, LA WEINER, SR VASEY, FB CROFFORD, LJ ODDIS, CV STARR, MR BRIDGES, AJ TARGOFF, IN GURLEY, RC MILLER, FW AF LOVE, LA WEINER, SR VASEY, FB CROFFORD, LJ ODDIS, CV STARR, MR BRIDGES, AJ TARGOFF, IN GURLEY, RC MILLER, FW TI CLINICAL AND IMMUNOGENETIC FEATURES OF WOMEN WHO DEVELOP MYOSITIS AFTER SILICONE IMPLANTS (MASI) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. UNIV S FLORIDA,TAMPA,FL 33620. NIAMS,BETHESDA,FL. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV MISSOURI,COLUMBIA,MO 65201. US FDA,CFSAN,BETHESDA,MD 20014. US FDA,CBER,BETHESDA,MD 20014. RI Crofford, Leslie/J-8010-2013 NR 0 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S46 EP S46 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800068 ER PT J AU LOVE, LA BURGESS, SH HILL, PC ODDIS, CV MEDSGER, TA LEFF, RL PLOTZ, PH REVEILLE, JD AMETT, FC TARGOFF, IN MILLER, FW AF LOVE, LA BURGESS, SH HILL, PC ODDIS, CV MEDSGER, TA LEFF, RL PLOTZ, PH REVEILLE, JD AMETT, FC TARGOFF, IN MILLER, FW TI GEOGRAPHICAL AND SEASONAL CLUSTERING IN THE ONSET OF IDIOPATHIC INFLAMMATORY MYOPATHY (IIM) IN GROUPS DEFINED BY MYOSITIS-SPECIFIC AUTOANTIBODIES (MSA) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US FDA,CBER,BETHESDA,MD 20014. NIAMS,BETHESDA,MD. UNIV PITTSBURGH,PITTSBURGH,PA 15260. NIH,BETHESDA,MD 20892. UNIV TEXAS,AUSTIN,TX 78712. NR 0 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S40 EP S40 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800031 ER PT J AU LOVELL, DJ HENDERSON, CJ SPECKER, B SIERRA, R ABRAMS, S YERGEY, A VIEIRA, N AF LOVELL, DJ HENDERSON, CJ SPECKER, B SIERRA, R ABRAMS, S YERGEY, A VIEIRA, N TI RELATIONSHIP OF TOTAL-BODY MINERAL DENSITY (TBBMD) AND PHYSICAL-ACTIVITY IN JRA - A CONTROLLED-STUDY USING DUAL ENERGY X-RAY ABSORPTOMETRY (DEXA) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV CINCINNATI,CINCINNATI,OH 45267. BAYLOR COLL MED,HOUSTON,TX 77030. NIH,BETHESDA,MD 20892. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S57 EP S57 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800135 ER PT J AU PALIOGIANNI, F AHUJA, SS YAMADA, H BALOW, JP BOUMPAS, DT AF PALIOGIANNI, F AHUJA, SS YAMADA, H BALOW, JP BOUMPAS, DT TI GLUCOCORTICOIDS (GC) INHIBIT T-CELL PROLIFERATION BY DOWN-REGULATING PROLIFERATIVE SIGNALS MEDIATED THROUGH BOTH T-CELL ANTIGEN AND INTERLEUKIN-2 RECEPTORS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S127 EP S127 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800545 ER PT J AU PALIOGIANNI, F RAPTIS, A AHUJA, SS NAJAR, S BALOW, JE BOUMPAS, DT AF PALIOGIANNI, F RAPTIS, A AHUJA, SS NAJAR, S BALOW, JE BOUMPAS, DT TI GLUCOCORTICOIDS (GC) INHIBIT THE NUCLEAR TRANSCRIPTION OF HUMAN INTERLEUKIN-2 GENE BY INTERFERING WITH NUCLEAR FACTORS AP-1 AND NF-AT SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S36 EP S36 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800007 ER PT J AU RABEN, N NICHOLS, RC JAIN, A AMIN, J HYDE, C LEFF, RL PLOTZ, PH AF RABEN, N NICHOLS, RC JAIN, A AMIN, J HYDE, C LEFF, RL PLOTZ, PH TI EXPRESSION OF RECOMBINANT HUMAN HISTIDYL TRANSFER-RNA SYNTHETASE, AN AUTOANTIGEN, IN BACULOVIRUS-TRANSFECTED INSECT CELLS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S170 EP S170 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800799 ER PT J AU ROTTEM, M FAUCI, AS HALLAHAN, CW KERR, GS LEBOVICS, RS LEAVITT, RY HOFFMAN, GS AF ROTTEM, M FAUCI, AS HALLAHAN, CW KERR, GS LEBOVICS, RS LEAVITT, RY HOFFMAN, GS TI WEGENERS GRANULOMATOSIS (WG) IN 23 CHILDREN - PRESENTATION AND LONG-TERM OUTCOME SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S56 EP S56 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800132 ER PT J AU RUBIN, L FALKWADE, J AMOS, C MARTIN, J GLADMAN, D SIMINOVITCH, K LITTLE, H RUBINSTEIN, J AF RUBIN, L FALKWADE, J AMOS, C MARTIN, J GLADMAN, D SIMINOVITCH, K LITTLE, H RUBINSTEIN, J TI LINKAGE ANALYSIS OF CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) REGION GENES IN ANKYLOSING-SPONDYLITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TORONTO,DEPT MED & RADIOL,TORONTO M5S 1A1,ONTARIO,CANADA. MEM UNIV NEWFOUNDLAND,DEPT MED,ST JOHNS A1C 5S7,NEWFOUNDLAND,CANADA. NIAMS,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S58 EP S58 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800142 ER PT J AU SANO, H ENGLEKA, K MATHERN, P HLA, T CROFFORD, LJ REMMERS, EF JELSEMA, CL GOLDMUNTZ, E MACIAG, T WILDER, RL AF SANO, H ENGLEKA, K MATHERN, P HLA, T CROFFORD, LJ REMMERS, EF JELSEMA, CL GOLDMUNTZ, E MACIAG, T WILDER, RL TI COEXPRESSION OF PHOSPHOTYROSINE-CONTAINING PROTEINS, PDGF-B AND FGF-1 INSITU IN SYNOVIAL TISSUES OF PATIENTS WITH RHEUMATOID-ARTHRITIS AND LEWIS RATS WITH ADJUVANT OR STREPTOCOCCAL CELL-WALL ARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMSD,ARTHRITUS & RHEUMAT BRANCH,BETHESDA,MD 20892. AMER RED CROSS,HOLLAND LAB,DEPT MOLEC BIOL,ROCKVILLE,MD 20855. RI Hla, Timothy/G-5873-2012; Crofford, Leslie/J-8010-2013 OI Hla, Timothy/0000-0001-8355-4065; NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S198 EP S198 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800963 ER PT J AU SCOTT, D CRAWFORD, K PUCINO, F BALOW, J EGGERMAN, T YARBORO, C SEBRING, N CRAWFORD, K BANKS, S HOEG, J KLIPPEL, J AF SCOTT, D CRAWFORD, K PUCINO, F BALOW, J EGGERMAN, T YARBORO, C SEBRING, N CRAWFORD, K BANKS, S HOEG, J KLIPPEL, J TI TREATMENT OF HYPERCHOLESTEROLEMIA IN SYSTEMIC LUPUS WITH LOVASTATIN SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S239 EP S239 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15801209 ER PT J AU SCOTT, WW LETHBRIDGECEJKU, M RICHLE, R WIGLEY, FM TOBIN, JD HOCHBERG, MC AF SCOTT, WW LETHBRIDGECEJKU, M RICHLE, R WIGLEY, FM TOBIN, JD HOCHBERG, MC TI RELIABILITY OF GRADING SCALES FOR INDIVIDUAL RADIOGRAPHIC FEATURES OF KNEE OSTEOARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S82 EP S82 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800282 ER PT J AU SILVER, R LUDWICKA, A OHBA, T BINGEL, S HARLEY, R HAMPTON, M MAIZE, J HEYES, M AF SILVER, R LUDWICKA, A OHBA, T BINGEL, S HARLEY, R HAMPTON, M MAIZE, J HEYES, M TI A MURINE MODEL FOR THE EOSINOPHILIA-MYALGIA-SYNDROME (EMS) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,CHARLESTON,SC 29425. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S66 EP S66 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800187 ER PT J AU TEMPLIN, DW BOYER, GS AF TEMPLIN, DW BOYER, GS TI EPIDEMIOLOGY OF RHEUMATOID-ARTHRITIS IN AN ALASKAN ESKIMO POPULATION SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 INDIAN HLTH SERV,ANCHROAGE,AK 99510. NIAMS,US USSR COOPERAT PROGRAM ARTHRIT & MUSCULOSKELETAL DIS,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S223 EP S223 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15801112 ER PT J AU TILLEY, BC AF TILLEY, BC TI RECRUITMENT STRATEGIES IN RHEUMATOID-ARTHRITIS (RA) CLINICAL-TRIALS - THE MINOCYCLINE IN RHEUMATOID-ARTHRITIS (MIRA) TRIAL EXPERIENCE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMSD,BETHESDA,MD. HENRY FORD HLTH SCI CTR,COORDINATING CTR,DETROIT,MI 48202. NR 0 TC 0 Z9 0 U1 3 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S341 EP S341 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15801592 ER PT J AU VOGELGESANG, S HEYES, MP SALAZAR, AM SFIKAKIS, PP LIPNICK, RN KLIPPLE, GL TSOKOS, GC AF VOGELGESANG, S HEYES, MP SALAZAR, AM SFIKAKIS, PP LIPNICK, RN KLIPPLE, GL TSOKOS, GC TI QUINOLINIC ACID (QA) LEVELS IN THE CEREBROSPINAL-FLUID (CSF) OF PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE) - PATHOGENETIC AND CLINICAL-SIGNIFICANCE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. CHILDRENS HOSP,NATL MED CTR,WASHINGTON,DC 20010. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1992 VL 35 IS 9 SU S BP S60 EP S60 PG 1 WC Rheumatology SC Rheumatology GA JR158 UT WOS:A1992JR15800155 ER PT J AU INSEL, TR AF INSEL, TR TI OXYTOCIN AND THE NEUROBIOLOGY OF ATTACHMENT SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Article ID MATERNAL-BEHAVIOR; PARAVENTRICULAR NUCLEUS; RATS; VASOPRESSIN; BRAIN; RECEPTORS; PRAIRIE; VOLES RP INSEL, TR (reprint author), NIMH,NEUROPHYSIOL LAB,POB 289,POOLESVILLE,MD 20837, USA. NR 23 TC 10 Z9 10 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD SEP PY 1992 VL 15 IS 3 BP 515 EP 516 PG 2 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA JN070 UT WOS:A1992JN07000035 PM 24924034 ER PT J AU TSUKAMOTO, K PALUMBO, A DISCHIA, M HEARING, VJ PROTA, G AF TSUKAMOTO, K PALUMBO, A DISCHIA, M HEARING, VJ PROTA, G TI 5,6-DIHYDROXYINDOLE-2-CARBOXYLIC ACID IS INCORPORATED IN MAMMALIAN MELANIN SO BIOCHEMICAL JOURNAL LA English DT Article ID METAL-IONS; DOPACHROME OXIDOREDUCTASE; MALIGNANT-MELANOMA; COATED VESICLES; TYROSINASE; BIOSYNTHESIS; PIGMENTATION; CELLS; REARRANGEMENT; PURIFICATION AB The role of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in the biosynthesis of melanins has been studied by using the incorporation of specifically radiolabelled melanogenic precursors into melanins formed by melanocytes growing in vitro and in vivo. Extracts of mouse melanocytes and intact viable melanocytes were found to incorporate into melanin from 25% to more than 60% of [1-C-14-]tyrosine. Melanins from melanoma tumours grown in mice were radiolabelled with 3,4-dihydroxy[1-C-14]phenylalanine, purified and chemoselectively decarboxylated. Determination of the (CO2)-C-14 evolved showed that at least 20% of the precursor incorporated in vivo retains the label in the form of non-aminoacidic aromatic-type carboxyl groups. These results provide the first unambiguous demonstration that DHICA is incorporated in physiologically relevant amounts in mammalian melanins. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. DEPT BIOCHEM,ZOOL STN,I-80121 NAPLES,ITALY. NAPLES UNIV,DEPT ORGAN & BIOL CHEM,I-80134 NAPLES,ITALY. RI d'Ischia, Marco/C-9837-2011 OI d'Ischia, Marco/0000-0002-7184-0029 NR 41 TC 62 Z9 62 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 1992 VL 286 BP 491 EP 495 PN 2 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM262 UT WOS:A1992JM26200026 PM 1530581 ER PT J AU WANG, LH BATTEY, JF WADA, E LIN, JT MANTEY, S COY, DH JENSEN, RT AF WANG, LH BATTEY, JF WADA, E LIN, JT MANTEY, S COY, DH JENSEN, RT TI ACTIVATION OF NEUROMEDIN B-PREFERRING BOMBESIN RECEPTORS ON RAT GLIOBLASTOMA C-6 CELLS INCREASES CELLULAR CA2+ AND PHOSPHOINOSITIDES SO BIOCHEMICAL JOURNAL LA English DT Article ID SWISS 3T3 CELLS; GASTRIN-RELEASING PEPTIDE; PANCREATIC ACINAR-CELLS; CENTRAL-NERVOUS-SYSTEM; LUNG-CANCER CELLS; ANTIMITOTIC ACTIVITY; INOSITOL PHOSPHATES; ANTAGONISTS; ANALOGS; BRAIN AB Recent cloning studies confirm the presence of two subtypes of bombesin (Bn) receptors. In contrast to the gastrin-releasing peptide (GRP)-preferring subtype, which has been widely studied, nothing is known about the cellular mechanisms of the neuromedin B (NMB)-preferring subtype, which occurs widely in the central nervous system and gastrointestinal tissues, partially because of the lack of a cell line with functional receptors. In the present study we have investigated Bn receptors on the rat glioblastoma cell line C-6, reported to contain mRNA of the NMB receptor subtype. Binding of I-125-[D-Tyr0]NMB to these cells was time- and temperature-dependent, saturable, reversible, and only inhibited by Bn receptor agonists or antagonists. For Bn receptor agonists the relative potencies were: NMB (1.7 nM) congruent-to litorin (3 nM) > ranatensin (8 nM) > Bn (19 nm) > neuromedin C (NMC) (210 nM) > GRP (500 nM). These relative affinities were almost identical to those for the NMB receptor subtype on rat oesophageal tissue and for Balb 3T3 cells stably transfected with the NMB receptor subtype. These potencies differed from those for the GRP receptor subtype on rat pancreatic acini [Bn congruent-to litorin (4 nM) > ranatensin, NMC, GRP (15-20 nm) much greater than NMB (351 nm)]. The relative potencies of four different classes of Bn receptor antagonists were compared. Results from C-6 tumour cells agreed closely with those for binding to the NMB receptor subtype on rat oesophageal tissue and in Balb 3T3 cells stably transfected with this receptor, and differed markedly from those for binding to the GRP receptor subtype on rat pancreatic acini. Four Bn receptor antagonists had a higher affinity for the GRP subtype {[D-Phe6]Bn-(6-13)ethyl ester (500 x), [D-Phe6][psi-13-14,Cpa14]Bn-(6-14) (70 x) (where psi-13-14 refers to the replacement of the -CONH- peptide bond between Leu13 and Met14 by -CH2NH2) [psi-13-14,Leu14]Bn, [D-Phe6]Bn-(6-13) propylamide (30 x)} and two had a higher affinity for the NMB subtype on C-6 cells and transfected cells {[D-Pro4,D-Trp7,9,10] substance P-(4-11) (9 x) and [Tyr4,D-Phe12]Bn (18 x)}. In C-6 tumour cells, Bn receptor agonists caused an increase in cytosolic Ca2+ and the generation of inositol phosphates. For both responses, NMB was more than 50-fold more potent than GRP. Neither NMB nor GRP increased cyclic AMP. These results demonstrate that the rat glioblastoma cell line C-6 possesses functional NMB-preferring Bn receptors, and agonist occupation activates phospholipase C, thus increasing cytosolic Ca2+ and inositol phosphate formation. Because the interaction of Bn-related peptides with C-6 cell receptors is identical with that reported in other tissues containing the mRNA for the NMB subtype, this cell line should prove useful in exploring further the cellular basis of action of the peptides that interact with this receptor in the central nervous system and various other tissues. C1 NIH,DIGEST DIS BRANCH,BLDG 10,ROOM 9C-103,BETHESDA,MD 20892. NIH,NEUROCHEM LAB,BETHESDA,MD 20892. TULANE UNIV,SCH MED,PEPTIDE RES LABS,NEW ORLEANS,LA 70112. NR 58 TC 52 Z9 53 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 1992 VL 286 BP 641 EP 648 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JM262 UT WOS:A1992JM26200050 PM 1326946 ER PT J AU LOH, YP AF LOH, YP TI MOLECULAR MECHANISMS OF BETA-ENDORPHIN BIOSYNTHESIS SO BIOCHEMICAL PHARMACOLOGY LA English DT Note ID PITUITARY INTERMEDIATE LOBE; OPIOMELANOCORTIN-CONVERTING ENZYME; MESSENGER-RNA LEVELS; PRO-OPIOMELANOCORTIN; RAT PITUITARY; SECRETORY VESICLES; ALPHA-MELANOTROPIN; PROCESSING ENZYMES; SEQUENCE-ANALYSIS; ATT20 CELLS RP LOH, YP (reprint author), NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BLDG 36,RM 2A21,BETHESDA,MD 20892, USA. NR 62 TC 35 Z9 35 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 1 PY 1992 VL 44 IS 5 BP 843 EP 849 DI 10.1016/0006-2952(92)90114-X PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JN588 UT WOS:A1992JN58800001 PM 1326963 ER PT J AU KAMATH, N GRABOWSKI, D FORD, J KERRIGAN, D POMMIER, Y GANAPATHI, R AF KAMATH, N GRABOWSKI, D FORD, J KERRIGAN, D POMMIER, Y GANAPATHI, R TI OVEREXPRESSION OF P-GLYCOPROTEIN AND ALTERATIONS IN TOPOISOMERASE-II IN P388 MOUSE LEUKEMIA-CELLS SELECTED INVIVO FOR RESISTANCE TO MITOXANTRONE SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID MULTIDRUG RESISTANCE; CELLULAR ACCUMULATION; CROSS-RESISTANCE; ANTITUMOR DRUGS; CYTO-TOXICITY; DNA; LINE; TRIFLUOPERAZINE; DOXORUBICIN; ADRIAMYCIN AB The overexpression of P-glycoprotein (PGP) and alterations in DNA topoisomerase II (TOPO II) were evaluated in mouse leukemia P388 cells selected i, vivo for mitoxantrone (MTT) resistance (P388/MTT) and compared to doxorubicin (DOX) resistant (P388/DOX) or vincristine (VCR) resistant (P388/VCR) models. Among a panel of TOPO II inhibitors which included etoposide (VP-16), DOX, MTT and 4'-[(9-acridinyl)-amino]methanesulfon-m-anisidide (m-AMSA), the relative resistance compared to parental sensitive P388/S cells was: P388/DOX > P388/MTT > P388/VCR. All the resistant sublines exhibited minimal cell kill (< 20%) at vincristine concentrations > 100-fold the IC50 for P388/S cells. In a soft-agar colony-forming assay, the modulation of cytotoxicity in P388/MTT cells by the calmodulin inhibitor trifluoperazine following a 3-hr drug treatment demonstrated a marked potentiation in cell kill with MTT, VP-16, DOX and m-AMSA but not VCR. Immunoblotting data revealed that while PGP was not detectable in P388/S cells, the overexpression of PGP was apparent in P388/MTT cells and the relative expression between the resistant sublines was: P388/DOX > P388/MTT > P388/VCR. Although the amount and DNA cleavage activity of TOPO II in nuclear extracts from P388/VCR cells were comparable to those in P388/S cells, they were markedly lower in both P388/DOX and P388/MTT cells. However, decatenation activity of TOPO II in nuclear extracts was comparable between the sensitive (P388/S) and resistant sublines (P388/MTT, P388/DOX, and P388/VCR). Results from the present study demonstrated that P388 cells selected for resistance to mitoxantrone exhibit changes in TOPO II and overexpression of PGP similar to P388/DOX cells, while vincristine resistant cells only overexpress PGP. Since therapeutic strategies are primarily designed to interfere with PGP-mediated drug efflux, the choice of agents for modulating resistance in tumors which overexpress PGP versus tumors which overexpress PGP with altered TOPO II could be different. C1 CLEVELAND CLIN FDN,RES INST,DEPT CANC BIOL,9500 EUCLID AVE,CLEVELAND,OH 44195. NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [R01CA35531] NR 33 TC 22 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 1 PY 1992 VL 44 IS 5 BP 937 EP 945 DI 10.1016/0006-2952(92)90126-4 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JN588 UT WOS:A1992JN58800013 PM 1356339 ER PT J AU HANSEN, JC WOLFFE, AP AF HANSEN, JC WOLFFE, AP TI INFLUENCE OF CHROMATIN FOLDING ON TRANSCRIPTION INITIATION AND ELONGATION BY RNA POLYMERASE-III SO BIOCHEMISTRY LA English DT Article ID NUCLEOSOME CORE PARTICLE; XENOPUS-LAEVIS OOCYTES; BALBIANI RING GENE; ASSEMBLED INVITRO; 5S-RNA GENES; DNA; HISTONES; SEQUENCES; COMPLEX; PROTEIN AB Nucleosomes were assembled onto either closed circular plasmids containing a single Xenopus 5S RNA gene or a linear tandemly repeated array of Lytechinus 5S RNA genes. Both chromatin templates were found to vary in their extent of compaction, depending upon the type and concentration of cation in solution. Compaction of these chromatin templates led to a significant inhibition of both transcription initiation and elongation by RNA polymerase III. Thus, the transcriptional repression observed after incorporation of genes into chromatin depends not only on occlusion of the promoter elements through direct contact with histones but also on compaction of nucleosomal arrays which occurs under the conditions of the transcription reactions. C1 NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM 131,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. FU NCRR NIH HHS [RR07187]; NIGMS NIH HHS [GM 45916] NR 67 TC 83 Z9 83 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 1 PY 1992 VL 31 IS 34 BP 7977 EP 7988 DI 10.1021/bi00149a032 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JL502 UT WOS:A1992JL50200032 PM 1510985 ER PT J AU BUTRYNSKI, JE JONES, TLZ BACKLUND, PS SPIEGEL, AM AF BUTRYNSKI, JE JONES, TLZ BACKLUND, PS SPIEGEL, AM TI DIFFERENTIAL ISOPRENYLATION OF CARBOXY-TERMINAL MUTANTS OF AN INHIBITORY G-PROTEIN ALPHA-SUBUNIT - NEITHER FARNESYLATION NOR GERANYLGERANYLATION IS SUFFICIENT FOR MEMBRANE ATTACHMENT SO BIOCHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING-PROTEINS; GTP-BINDING; SIGNAL TRANSDUCTION; GAMMA-SUBUNIT; RAS PROTEINS; BOVINE BRAIN; METHYL-ESTER; BETA-GAMMA; IDENTIFICATION; P21RAS AB To determine the effect of protein isoprenylation with farnesyl vs geranylgeranyl groups on membrane association in vivo, COS cells were transfected with cDNAs encoding the wild-type G-protein alpha(i)1 (WT) subunit, the soluble nonmyristoylated G-protein alpha(i)1 glycine to alanine mutant (GA), a double mutant in which the carboxy-terminal residues CGLF of GA were mutated to CVLS (GA-CVLS), and a double mutant in which the carboxy terminus of GA was mutated to CALL (GA-CALL). As opposed to the WT and GA proteins, the GA-CVLS and GA-CALL proteins were not pertussis toxin substrates nor were they recognized by antibodies that recognize the nonmutated alpha(i)1 carboxy terminus. Only the GA-CVLS and GA-CALL proteins incorporated [H-3]mevalonate in the form of a farnesyl and a geranylgeranyl moiety, respectively. Subcellular localization, as assessed by immunoblotting and immunoprecipitation, revealed that the WT protein localizes almost exclusively to the membrane fraction, whereas the GA, GA-CVLS, and GA-CALL proteins localize predominantly to the soluble fraction. The soluble GA-CVLS and GA-CALL proteins were not carboxyl methylated, but the small amount localized to the membrane was partially carboxyl methylated. These results indicate that neither farnesylation nor geranylgeranylation is sufficient alone to lead to membrane association. C1 NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,ROOM 8C101,BETHESDA,MD 20892. NIMH,GEN & COMPARAT BIOCHEM LAB,BETHESDA,MD 20892. NR 44 TC 18 Z9 18 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 1 PY 1992 VL 31 IS 34 BP 8030 EP 8035 DI 10.1021/bi00149a037 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JL502 UT WOS:A1992JL50200037 PM 1510988 ER PT J AU VALDIVIA, HH MARTIN, BM ESCOBAR, L POSSANI, LD AF VALDIVIA, HH MARTIN, BM ESCOBAR, L POSSANI, LD TI NOXIUSTOXIN AND LEIURUTOXIN-III, 2 HOMOLOGOUS PEPTIDE TOXINS WITH BINDING-PROPERTIES TO SYNAPTOSOMAL MEMBRANE K+ CHANNELS SO BIOCHEMISTRY INTERNATIONAL LA English DT Article ID SCORPION CENTRUROIDES-NOXIUS; POTASSIUM CHANNEL; VENOM; BLOCKING; CHARYBDOTOXIN; PURIFICATION; INHIBITOR; UNIQUE; POTENT C1 UNIV NACL AUTONOMA MEXICO,INST BIOTECNOL,DEPT BIOQUIM,APARTADO POSTAL 510-3,CUERNAVACA 62271,MORELOS,MEXICO. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET UNIT,BETHESDA,MD 20892. RI Possani, Lourival/J-2397-2013 NR 15 TC 15 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 0158-5231 J9 BIOCHEM INT PD SEP PY 1992 VL 27 IS 6 BP 953 EP 962 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JQ094 UT WOS:A1992JQ09400001 PM 1280139 ER PT J AU SUDO, K MAEKAWA, M SHIOYA, M IKEDA, K TAKAHASHI, N ISOGAI, Y LI, SSL KANNO, T MACHIDA, K TORIUMI, J AF SUDO, K MAEKAWA, M SHIOYA, M IKEDA, K TAKAHASHI, N ISOGAI, Y LI, SSL KANNO, T MACHIDA, K TORIUMI, J TI MOLECULAR ANALYSIS OF GENETIC MUTATION IN ELECTROPHORETIC VARIANT OF HUMAN LACTATE DEHYDROGENASE-A(M) SUBUNIT SO BIOCHEMISTRY INTERNATIONAL LA English DT Article ID CHROMOSOME-11; TESTIS; MUSCLE; HEART C1 HAMAMATSU UNIV SCH MED, DEPT LAB MED, HAMAMATSU, SHIZUOKA 43131, JAPAN. JIKEI UNIV, CENT LAB, MINATO KU, TOKYO 105, JAPAN. JIKEI UNIV, DEPT INTERNAL MED 3, MINATO KU, TOKYO 105, JAPAN. NIEHS, GENET LAB, RES TRIANGLE PK, NC 27709 USA. RP SUDO, K (reprint author), JIKEI UNIV, DAISAN HOSP, SCH MED, DEPT LAB MED, 4-11-1 IZUMI HONCHO, KOMAE 201, JAPAN. NR 21 TC 4 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE, NSW 2204, AUSTRALIA SN 0158-5231 J9 BIOCHEM INT PD SEP PY 1992 VL 27 IS 6 BP 1051 EP 1057 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JQ094 UT WOS:A1992JQ09400012 PM 1445373 ER PT J AU HAYES, JJ WOLFFE, AP AF HAYES, JJ WOLFFE, AP TI THE INTERACTION OF TRANSCRIPTION FACTORS WITH NUCLEOSOMAL DNA SO BIOESSAYS LA English DT Review ID TUMOR VIRUS PROMOTER; RNA GENE; GLUCOCORTICOID RECEPTOR; XENOPUS-LAEVIS; FACTOR-IIIA; 5S RNA; HISTONE OCTAMER; CORE PARTICLE; CHROMATIN; SEQUENCE AB Nucleosome positioning is proposed to have an essential role in facilitating the regulated transcription of eukaryotic genes. Some transcription factors can bind to DNA when it is appropriately wrapped around the histone core, others cannot bind due to the severe deformation of DNA structure. The staged assembly of nucleosomes and positioning of histone-DNA contacts away from promoter elements can facilitate the access of transcription factors to DNA. Positioned nucleosomes can also facilitate transcription through providing the appropriate scaffolding to bring regulatory factors bound at dispersed sites into juxtaposition. RP HAYES, JJ (reprint author), NICHHD,MOLEC EMBRYOL LAB,BLDG 6,RM 131,BETHESDA,MD 20892, USA. NR 49 TC 79 Z9 79 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD SEP PY 1992 VL 14 IS 9 BP 597 EP 603 DI 10.1002/bies.950140905 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA JR767 UT WOS:A1992JR76700003 PM 1365915 ER PT J AU ROUAULT, TA HAILE, DJ DOWNEY, WE PHILPOTT, CC TANG, C SAMANIEGO, F CHIN, J PAUL, I ORLOFF, D HARFORD, JB KLAUSNER, RD AF ROUAULT, TA HAILE, DJ DOWNEY, WE PHILPOTT, CC TANG, C SAMANIEGO, F CHIN, J PAUL, I ORLOFF, D HARFORD, JB KLAUSNER, RD TI AN IRON SULFUR CLUSTER PLAYS A NOVEL REGULATORY ROLE IN THE IRON-RESPONSIVE ELEMENT BINDING-PROTEIN SO BIOMETALS LA English DT Review DE ACONITASE; FERRITIN; IRON-RESPONSIVE ELEMENT BINDING PROTEIN; IRON-RESPONSIVE ELEMENTS; IRON SULFUR CLUSTERS; RNA BINDING ID FERRITIN MESSENGER-RNA; TRANSLATIONAL REGULATION; AFFINITY PURIFICATION; UNTRANSLATED REGION; HEART ACONITASE; IRE-BP; EXPRESSION; SEQUENCE; GENE; IDENTIFICATION AB Post-transcriptional regulation of genes important in iron metabolism, ferritin and the transferrin receptor (TfR), is achieved through regulated binding of a cytosolic protein, the iron-responsive element binding protein (IRE-BP), to RNA stem-loop motifs known as iron-responsive elements (IREs). Binding of the IRE-BP represses ferritin translation and represses degradation of the TfR mRNA. The IRE-BP senses iron levels and accordingly modifies binding to IREs through a novel sensing mechanism. An iron-sulfur cluster of the IRE-BP reversibly binds iron; when cytosolic iron levels are depleted, the cluster becomes depleted of iron and the IRE-BP acquires the capacity to bind IREs. When cytosolic iron levels are replete, the IRE-BP loses RNA binding capacity, but acquires enzymatic activity as a functional aconitase. RNA binding and aconitase activity are mutually exclusive activities of the IRE-BP, and the state of the iron-sulfur cluster determines how the IRE-BP will function. RP ROUAULT, TA (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BLDG 18,BETHESDA,MD 20892, USA. NR 53 TC 76 Z9 76 U1 1 U2 7 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0966-0844 J9 BIOMETALS JI Biometals PD FAL PY 1992 VL 5 IS 3 BP 131 EP 140 DI 10.1007/BF01061319 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JQ043 UT WOS:A1992JQ04300001 PM 1421965 ER PT J AU ZUCKER, D WITTES, J AF ZUCKER, D WITTES, J TI TESTING THE EFFECT OF TREATMENT IN EXPERIMENTS WITH CORRELATED BINARY OUTCOMES SO BIOMETRICS LA English DT Article DE ASYMPTOTIC RELATIVE EFFICIENCY; CORRELATED BINARY DATA; MANTEL-HAENSZEL TEST; RANDOMIZED EXPERIMENT; RATIO ESTIMATE; SUMMARY SCORE STATISTICS ID REGRESSION; OPHTHALMOLOGY AB This paper considers the problem of testing for treatment effect in a randomized experiment with correlated binary outcomes, representing success or failure for different "parts" of a randomized unit. Attention is restricted to tests that are based on a summary score for each individual randomized, and thus are valid regardless of the precise nature of the correlation among parts. The focus is on the efficiency of such tests under various correlation structures, with special emphasis on the case in which the correlation among parts within an individual differs across treatment groups. A class of summary score statistics is defined, and optimal testing is discussed for some simple situations. Three potential general-purpose tests also are described: (1) the ratio estimate test discussed by Henderson et al. (1988, Controlled Clinical Trials 9, 189-205); (2) a modified ratio estimate test with adjusted weighting based on the within-individual correlation between parts; (3) a test defined by applying the Mantel-Haenszel procedure to the proportion of individuals with at least one failure, stratifying by the number of parts. For these general-purpose tests, numerical calculations of asymptotic efficiency are presented under a wide range of designs and correlation structures. On the basis of these results, some practical recommendations for choosing a test are made. C1 STAT COLLABORAT,1816 JEFFERSON PL NW,WASHINGTON,DC 20036. NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. NR 19 TC 15 Z9 15 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1992 VL 48 IS 3 BP 695 EP 710 DI 10.2307/2532337 PG 16 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA JN584 UT WOS:A1992JN58400004 PM 1420835 ER PT J AU WU, MC LAN, KKG AF WU, MC LAN, KKG TI SEQUENTIAL MONITORING FOR COMPARISON OF CHANGES IN A RESPONSE VARIABLE IN CLINICAL-STUDIES SO BIOMETRICS LA English DT Article DE AREA UNDER THE RESPONSE CURVE; INFORMATIVE CENSORING; LINEAR RANDOM EFFECTS; POLYNOMIAL RESPONSE CURVES; SPENDING FUNCTION ID TRIALS; DESIGN; MODELS; TESTS AB The spending function approach proposed by Lan and DeMets (1983, Biometrika 70, 659-663) for sequential monitoring of clinical trials is applied to situations where comparison of changes in a continuous response variable between two groups is the primary concern. Death, loss to follow-up, and missed visits could cause follow-up measurements to be right-censored or missing for some participants. Furthermore, the probability of being censored may be dependent on the parameter value of the response variable (informative censoring). We propose to compare treatment effects by comparing areas under the expected response change curves between the two groups. When the response curves are linear as a function of time in both groups, this comparison is equivalent to comparing the rates of change in the response variable. Covariances of the sequential test statistics are derived. Conditions for having independent increments are presented. For studies designed to evaluate long-term treatment effects, spending functions obtained by shifting the usual spending functions (Kim and DeMets, 1987, Biometrika 74, 149-154) to the right and then rescaling to the remaining interval are also proposed. Such a shifted spending function is applied to the monitoring plan for the Lung Health Study (Anthonisen, 1989, American Review of Respiratory Diseases 140, 871-872). C1 GEORGE WASHINGTON UNIV,DEPT STAT COMP & INFORMAT SYST,WASHINGTON,DC 20052. RP WU, MC (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BIOSTAT RES BRANCH,BETHESDA,MD 20892, USA. NR 23 TC 33 Z9 33 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1992 VL 48 IS 3 BP 765 EP 779 DI 10.2307/2532343 PG 15 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA JN584 UT WOS:A1992JN58400010 PM 1420840 ER PT J AU ZUCKER, DM AF ZUCKER, DM TI THE EFFICIENCY OF A WEIGHTED LOG-RANK TEST UNDER A PERCENT ERROR MISSPECIFICATION MODEL FOR THE LOG HAZARD RATIO SO BIOMETRICS LA English DT Note DE CLINICAL TRIAL; MISSPECIFICATION MODEL; RELATIVE EFFICIENCY; WEIGHTED LOG-RANK STATISTIC ID SURVIVAL DISTRIBUTIONS AB For comparison of two survival distributions, it is natural to use a weighted log-rank test with weight function given by the log hazard ratio function that is anticipated a priori. This paper investigates the efficiency of this test when the a priori estimate of the log hazard ratio is subject to a specified percentage error. The test is shown to be the maximin efficiency robust test over the class of alternatives in question and a simple expression for the maximin efficiency is established. RP ZUCKER, DM (reprint author), NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892, USA. NR 18 TC 7 Z9 7 U1 1 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1992 VL 48 IS 3 BP 893 EP 899 DI 10.2307/2532355 PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA JN584 UT WOS:A1992JN58400022 PM 1420846 ER PT J AU ODELL, PM ANDERSON, KM DAGOSTINO, RB AF ODELL, PM ANDERSON, KM DAGOSTINO, RB TI MAXIMUM-LIKELIHOOD-ESTIMATION FOR INTERVAL-CENSORED DATA USING A WEIBULL-BASED ACCELERATED FAILURE TIME MODEL SO BIOMETRICS LA English DT Article DE ACCELERATED FAILURE TIME MODEL; INTERVAL CENSORING; WEIBULL MODEL AB The accelerated failure time regression model is most commonly used with right-censored survival data. This report studies the use of a Weibull-based accelerated failure time regression model when left- and interval-censored data are also observed. Two alternative methods of analysis are considered. First, the maximum likelihood estimates (MLEs) for the observed censoring pattern are computed. These are compared with estimates where midpoints are substituted for left- and interval-censored data (midpoint estimator, or MDE). Simulation studies indicate that for relatively large samples there are many instances when the MLE is superior to the MDE. For samples where the hazard rate is flat or nearly so, or where the percentage of interval-censored data is small, the MDE is adequate. An example using Framingham Heart Study data is discussed. C1 CENTOCOR INC,MALVERN,PA 19355. BOSTON UNIV,111 CUMMINGTON ST,BOSTON,MA 02118. NHLBI,FRAMINGHAM,MA. RP ODELL, PM (reprint author), BRYANT COLL,SMITHFIELD,RI 02917, USA. FU NHLBI NIH HHS [R01HL41423-02] NR 11 TC 92 Z9 97 U1 1 U2 18 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1992 VL 48 IS 3 BP 951 EP 959 DI 10.2307/2532360 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA JN584 UT WOS:A1992JN58400027 PM 1420849 ER PT J AU YU, KF AF YU, KF TI ON ESTIMATING STANDARDIZED RISK DIFFERENCES FROM ODDS RATIOS SO BIOMETRICS LA English DT Article DE EPIDEMIOLOGIC METHODS; MANTEL-HAENSZEL ESTIMATOR; ODDS RATIO; RELATIVE RISK; 2X2 TABLES AB An estimator proposed by Greenland and Holland (1991, Biometrics 47, 319-322) for a standardized risk difference parameter is shown to be a maximum likelihood estimator if the consistent estimator of the common odds ratio is appropriately chosen. The statistical problem under consideration is reparameterized. Likelihood equations are derived. RP YU, KF (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 U1 1 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1992 VL 48 IS 3 BP 961 EP 964 DI 10.2307/2532361 PG 4 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA JN584 UT WOS:A1992JN58400028 PM 1420850 ER PT J AU DONG, C CHADWICK, RS SCHECHTER, AN AF DONG, C CHADWICK, RS SCHECHTER, AN TI INFLUENCE OF SICKLE HEMOGLOBIN POLYMERIZATION AND MEMBRANE-PROPERTIES ON DEFORMABILITY OF SICKLE ERYTHROCYTES IN THE MICROCIRCULATION SO BIOPHYSICAL JOURNAL LA English DT Article ID RED-BLOOD-CELLS; MECHANICAL-PROPERTIES; VISCOELASTIC PROPERTIES; HEMOLYTIC-ANEMIAS; OXYGEN-TENSION; DISEASE; FLOW; FILTRATION; FILTERABILITY; DEOXYGENATION AB The rheological properties of normal erythrocytes appear to be largely determined by those of the red cell membrane. In sickle cell disease, the intracellular polymerization of sickle hemoglobin upon deoxygenation leads to a marked increase in intracellular viscosity and elastic stiffness as well as having indirect effects on the cell membrane. To estimate the components of abnormal cell rheology due to the polymerization process and that due to the membrane abnormalities, we have developed a simple mathematical model of whole cell deformability in narrow vessels. This model uses hydrodynamic lubrication theory to describe the pulsatile flow in the gap between a cell and the vessel wall. The interior of the cell is modeled as a Voigt viscoelastic solid with parameters for the viscous and elastic moduli, while the membrane is assigned an elastic shear modulus. In response to an oscillatory fluid shear stress, the cell-modeled as a cylinder of constant volume and surface area-undergoes a conical deformation which may be calculated, We use published values of normal and sickle cell membrane elastic modulus and of sickle hemoglobin viscous and elastic moduli as a function of oxygen saturation, to estimate normalized tip displacement, d/h(o), and relative hydrodynamic resistance, R(r), as a function of polymer fraction of hemoglobin for sickle erythrocytes. These results show the transition from membrane to internal polymer dominance of deformability as oxygen saturation is lowered. More detailed experimental data, including those at other oscillatory frequencies and for cells with higher concentrations of hemoglobin S, are needed to apply fully this approach to understanding the deformability of sickle erythrocytes in the microcirculation. The model should be useful for reconciling the vast and disparate sets of data available on the abnormal properties of sickle cell hemoglobin and sickle erythrocyte membranes, the two main factors that lead to pathology in patients with this disease. C1 NIDDKD,CHEM BIOL LAB,BETHESDA,MD 20892. RP DONG, C (reprint author), NIDDKD,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 52 TC 20 Z9 21 U1 1 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1992 VL 63 IS 3 BP 774 EP 783 PG 10 WC Biophysics SC Biophysics GA JP021 UT WOS:A1992JP02100018 PM 1420913 ER PT J AU LAZAROUS, DF SHOU, M UNGER, EF AF LAZAROUS, DF SHOU, M UNGER, EF TI COMBINED BROMODEOXYURIDINE IMMUNOHISTOCHEMISTRY AND MASSON TRICHROME STAINING - FACILITATED DETECTION OF CELL-PROLIFERATION IN VIABLE VS INFARCTED MYOCARDIUM SO BIOTECHNIC & HISTOCHEMISTRY LA English DT Article DE BROMODEOXYURIDINE IMMUNOHISTOCHEMISTRY; MASSON TRICHROME COUNTERSTAIN; MYOCARDIUM; MYOCARDIAL INFARCTION ID MONOCLONAL-ANTIBODY AB Cells in the S-phase of the cell cycle can be identified in tissue sections by immunohistochemical localization of the thymidine analogue bromodeoxyuridine (BrdU). Generally, a single counterstain is used to visualize the underlying tissue; however, interpretation of morphologic detail is often difficult. We have utilized BrdU to localize proliferating cells in myocardium exposed to angiogenic mitogens. To facilitate identification of labelled nuclei in the context of infarcted vs. viable myocardium, BrdU unmunohistochemistry was followed by a modified Masson trichrome stain. The time of exposure to the counterstains and the wash protocol were re-revised, permitting clear identification of the labelled brown nuclei against a background of red viable myocardium vs. blue infarct. The combined technique also provides color contrast suitable for computer-based image analysis. RP LAZAROUS, DF (reprint author), NHLBI,CARDIOL BRANCH,EXPTL PHYSIOL & PHARMACOL LAB,9000 ROCKVILLE PIKE,BLDG 10,BETHESDA,MD 20892, USA. NR 6 TC 7 Z9 7 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1052-0295 J9 BIOTECH HISTOCHEM JI Biotech. Histochem. PD SEP PY 1992 VL 67 IS 5 BP 253 EP 255 DI 10.3109/10520299209110032 PG 3 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA JP236 UT WOS:A1992JP23600001 PM 1284404 ER PT J AU LOUGHRAN, TP COYLE, T SHERMAN, MP STARKEBAUM, G EHRLICH, GD RUSCETTI, FW POIESZ, BJ AF LOUGHRAN, TP COYLE, T SHERMAN, MP STARKEBAUM, G EHRLICH, GD RUSCETTI, FW POIESZ, BJ TI DETECTION OF HUMAN T-CELL LEUKEMIA LYMPHOMA VIRUS, TYPE-II, IN A PATIENT WITH LARGE GRANULAR LYMPHOCYTE LEUKEMIA SO BLOOD LA English DT Note ID LYMPHOPROLIFERATIVE DISEASE; INFECTION; ASSOCIATION; INDIVIDUALS; EXPRESSION; BLOOD C1 VET ADM MED CTR,SEATTLE,WA 98108. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. SUNY COLL ENVIRONM SCI & FORESTRY,SYRACUSE,NY 13210. NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21701. FU NCI NIH HHS [CA 46903, CA 54552]; NHLBI NIH HHS [HL 43602] NR 17 TC 120 Z9 120 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1992 VL 80 IS 5 BP 1116 EP 1119 PG 4 WC Hematology SC Hematology GA JL367 UT WOS:A1992JL36700002 PM 1355373 ER PT J AU ROBINSON, PJ NORONHA, J DEGEORGE, JJ FREED, LM NARIAI, T RAPOPORT, SI AF ROBINSON, PJ NORONHA, J DEGEORGE, JJ FREED, LM NARIAI, T RAPOPORT, SI TI A QUANTITATIVE METHOD FOR MEASURING REGIONAL INVIVO FATTY-ACID INCORPORATION INTO AND TURNOVER WITHIN BRAIN PHOSPHOLIPIDS - REVIEW AND CRITICAL ANALYSIS SO BRAIN RESEARCH REVIEWS LA English DT Review DE BRAIN; FATTY ACID; NEUROPLASTICITY; QUANTITATIVE AUTORADIOGRAPHY; TRACER KINETICS; LIPID; SYNTHESIS; TURNOVER; PHOSPHOLIPID; PALMITATE; ARACHIDONATE; DOCOSAHEXAENOATE; TUMOR; IMAGING ID CEREBRAL GLUCOSE-UTILIZATION; PLASMA C-14 PALMITATE; NUCLEUS BASALIS MAGNOCELLULARIS; ANTEROVENTRAL COCHLEAR NUCLEUS; HIPPOCAMPUS FOLLOWING ISCHEMIA; DELAYED NEURONAL DEATH; CENTRAL NERVOUS-SYSTEM; C62B GLIOMA-CELLS; RAT-BRAIN; HYPOGLOSSAL NUCLEUS C1 NIA, NEUROSCI LAB, BLDG 10, RM 6C-103, BETHESDA, MD 20892 USA. NR 154 TC 216 Z9 217 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 EI 1872-6321 J9 BRAIN RES REV JI Brain Res. Rev. PD SEP-DEC PY 1992 VL 17 IS 3 BP 187 EP 214 DI 10.1016/0165-0173(92)90016-F PG 28 WC Neurosciences SC Neurosciences & Neurology GA JZ657 UT WOS:A1992JZ65700001 PM 1467810 ER PT J AU MOLCHAN, SE MARTINEZ, RA HILL, JL WEINGARTNER, HJ THOMPSON, K VITIELLO, B SUNDERLAND, T AF MOLCHAN, SE MARTINEZ, RA HILL, JL WEINGARTNER, HJ THOMPSON, K VITIELLO, B SUNDERLAND, T TI INCREASED COGNITIVE SENSITIVITY TO SCOPOLAMINE WITH AGE AND A PERSPECTIVE ON THE SCOPOLAMINE MODEL SO BRAIN RESEARCH REVIEWS LA English DT Review DE ALZHEIMERS DISEASE; SCOPOLAMINE; AGING; ACETYLCHOLINE; MEMORY ID ALZHEIMER-TYPE DEMENTIA; HEALTHY-YOUNG VOLUNTEERS; CHOLINERGIC NEURONS; SENILE DEMENTIA; WORKING MEMORY; CEREBRAL-CORTEX; INDUCED AMNESIA; VERBAL MEMORY; DISEASE; RECEPTORS C1 NIAAA,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,GERIATR PSYCHOPHARMACOL UNIT,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BIOSTAT UNIT,BETHESDA,MD 20892. NR 111 TC 157 Z9 159 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD SEP-DEC PY 1992 VL 17 IS 3 BP 215 EP 226 DI 10.1016/0165-0173(92)90017-G PG 12 WC Neurosciences SC Neurosciences & Neurology GA JZ657 UT WOS:A1992JZ65700002 PM 1467811 ER PT J AU LEWIS, JF SPIRITO, P PELLICCIA, A MARON, BJ AF LEWIS, JF SPIRITO, P PELLICCIA, A MARON, BJ TI USEFULNESS OF DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLIC FILLING IN DISTINGUISHING ATHLETES HEART FROM HYPERTROPHIC CARDIOMYOPATHY SO BRITISH HEART JOURNAL LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; FLOW VELOCITY PATTERNS; PHYSIOLOGIC HYPERTROPHY; CLINICAL MANIFESTATIONS; CARDIAC-HYPERTROPHY; PATHO-PHYSIOLOGY; M-MODE; INTERRELATIONS; DIMENSIONS; MECHANICS AB Objective-In some athletes with a substantial increase in left ventricular wall thickness, it may be difficult to distinguish with certainty physiological hypertrophy due to athletic training from hypertrophic cardiomyopathy. The purpose of the present investigation was to determine whether assessment of left ventricular filling could differentiate between these two conditions. Design-Doppler echocardiography was used to obtain transmitral flow velocity waveforms from which indices of left ventricular diastolic filling were measured. Normal values were from 35 previously studied control subjects. Setting-Athletes were selected mostly from the Institute of Sports Science (Rome, Italy), and patients with hypertrophic cardiomyopathy were studied at the National Institutes of Health (Bethesda, Maryland). Participants-The athlete group comprised 16 young competitive athletes with an increase in left ventricular wall thickness (range 13-16 mm; mean 14). For comparison, 12 symptom free patients with non-obstructive hypertrophic cardiomyopathy were selected because their ages and degree of hypertrophy were similar to those of the athletes. Results-In the athlete group, values for deceleration of flow velocity in early diastole, peak early and late diastolic flow velocities, and their ratio were not significantly different from those obtained in untrained normal subjects; furthermore, Doppler diastolic indices were normal in each of the 16 athletes. Conversely, in patients with hypertrophic cardiomyopathy, mean values for Doppler diastolic indices were significantly different from both normal subjects and athletics (p = 0.01 to 0.003), and one or more indices were abnormal in 10 (83%) of the 12 patients. Conclusions-Doppler echocardiographic indices of left ventricular filling may aid in distinguishing between pronounced physiological hypertrophy due to athletic training and pathological hypertrophy associated with hypertrophic cardiomyopathy. C1 HOWARD UNIV,COLL MED,DEPT MED,DIV CARDIOL,WASHINGTON,DC 20001. ITALIAN NATL OLYMP COMM,INST SPORTS SCI,DEPT MED,ROME,ITALY. RP LEWIS, JF (reprint author), NHLBI,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL 01984] NR 38 TC 95 Z9 97 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-0769 J9 BRIT HEART J JI Br. Heart J. PD SEP PY 1992 VL 68 IS 3 BP 296 EP 300 PG 5 WC Cardiac & Cardiovascular Systems; History & Philosophy Of Science SC Cardiovascular System & Cardiology; History & Philosophy of Science GA JL978 UT WOS:A1992JL97800011 PM 1389762 ER PT J AU GFROERER, J BRODSKY, M AF GFROERER, J BRODSKY, M TI THE INCIDENCE OF ILLICIT DRUG-USE IN THE UNITED-STATES, 1962-1989 SO BRITISH JOURNAL OF ADDICTION LA English DT Article AB Epidemiological descriptions of drug abuse in the US in the last three decades have generally not included data on the patterns and trends in the incidence of illicit drug use (i.e. new users). In this paper, estimates of illicit drug use incidence are presented, based on retrospective data from the National Household Survey on Drug Abuse. Incidence of marijuana use began increasing in the 1960s and reached a peak in 1973, after which a continuing decline was seen. Cocaine use incidence began to increase in the late 1960s and reached a peak in 1982, then declined. RP GFROERER, J (reprint author), NIDA,DIV EPIDEMIOL & PREVENT RES,5600 FISHERS LANE,ROCKWALL 2 BLDG,SUITE 615,ROCKVILLE,MD 20857, USA. NR 8 TC 52 Z9 52 U1 0 U2 2 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0952-0481 J9 BRIT J ADDICT PD SEP PY 1992 VL 87 IS 9 BP 1345 EP 1351 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA JM470 UT WOS:A1992JM47000012 PM 1392556 ER PT J AU GIACCONE, G BROERS, J JENSEN, S FRIDMAN, RI LINNOILA, R GAZDAR, AF AF GIACCONE, G BROERS, J JENSEN, S FRIDMAN, RI LINNOILA, R GAZDAR, AF TI INCREASED EXPRESSION OF DIFFERENTIATION MARKERS CAN ACCOMPANY LAMININ-INDUCED ATTACHMENT OF SMALL-CELL LUNG-CANCER CELLS SO BRITISH JOURNAL OF CANCER LA English DT Article ID INTERMEDIATE FILAMENT PROTEINS; GASTRIN-RELEASING PEPTIDE; DNA TOPOISOMERASE-II; MONOCLONAL-ANTIBODY; RETINOIC ACID; GENE FAMILY; NEUROFILAMENT SUBUNIT; MESSENGER-RNAS; GROWTH-FACTOR; LINES AB We investigated the interaction between human lung cancer cells, laminin, and several differentiating agents. When grown on laminin coated substrate eight out of 11 small cell lung cancer (SCLC) cell lines exhibited attachment to laminin and three had extensive outgrowth of long neurite-like processes. Of seven non-small cell lung cancer cell lines. selected for their in vitro anchorage-independent growth, attachment was observed in only three cell lines, and process formation was far less extensive than in SCLC cell lines. Among several differentiating agents, only dcAMP, which alone induced attachment and some process formation, increased laminin-mediated attachment and process formation of two SCLC cell tines, NCI-N417 a variant cell line, and NCI-H345, a classic cell line. The expression of several neuroendocrine and neuronal markers was investigated in these two SCLC cell lines. The expression of the light subunit of neurofilaments increased in NCI-N417 within 3 to 4 days of seeding, while NCI-H345 exhibited approximately 5 fold increase in expression of the GRP gene and a 3 fold increase expression of the beta-actin gene. The expression of a number of other neuroendocrine and neuronal markers did not change following growth on laminin. The doubling times remained unchanged independent of the presence of and attachment to laminin while topoisomerase II gene expression levels in NCI-N417 cells decreased approximately 5 fold when cells were growing on laminin. C1 NCI,NAVY MED ONCOL,BETHESDA,MD 20892. NIDR,DEV BIOL & ANOMALIES LAB,BETHESDA,MD 20892. RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 44 TC 9 Z9 9 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP PY 1992 VL 66 IS 3 BP 488 EP 495 DI 10.1038/bjc.1992.301 PG 8 WC Oncology SC Oncology GA JM909 UT WOS:A1992JM90900013 PM 1325826 ER PT J AU PUTNAM, FW AF PUTNAM, FW TI MULTIPLE PERSONALITY-DISORDER SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Letter RP PUTNAM, FW (reprint author), NIMH,DEV PSYCHOL LAB,BETHESDA,MD 20892, USA. NR 4 TC 7 Z9 7 U1 0 U2 0 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD SEP PY 1992 VL 161 BP 415 EP 416 PG 2 WC Psychiatry SC Psychiatry GA JN174 UT WOS:A1992JN17400024 PM 1489435 ER PT J AU HOROWITZ, ME TSOKOS, MG DELANEY, TF AF HOROWITZ, ME TSOKOS, MG DELANEY, TF TI EWINGS-SARCOMA SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article AB Important advances have been made during the last two decades in the treatment and understanding of Ewing's sarcoma, the second most common primary bone cancer of childhood. This article reviews the clinical features, diagnostic evaluation, and treatment of the disease. RP HOROWITZ, ME (reprint author), NCI,PEDIAT BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 15 Z9 15 U1 0 U2 0 PU AMER CANCER SOC PI NEW YORK PA C/O JB LIPPINCOTT CO 1180 AVE OF THE AMERICAS 6TH FLOOR, NEW YORK, NY 10036 SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD SEP-OCT PY 1992 VL 42 IS 5 BP 300 EP 320 DI 10.3322/canjclin.42.5.300 PG 21 WC Oncology SC Oncology GA JL932 UT WOS:A1992JL93200005 PM 1515969 ER PT J AU LEVINE, PH POCINKI, AG MADIGAN, P BALE, S AF LEVINE, PH POCINKI, AG MADIGAN, P BALE, S TI FAMILIAL NASOPHARYNGEAL CARCINOMA IN PATIENTS WHO ARE NOT CHINESE SO CANCER LA English DT Article DE NASOPHARYNGEAL CARCINOMA; FAMILIAL CANCER; EPSTEIN-BARR VIRUS ID EPSTEIN-BARR VIRUS; IMMUNOGENETIC ASPECTS; HLA; RISK AB Background. Nasopharyngeal carcinoma [NPC] is a malignancy that is prominent in Cantonese Chinese people. It is presumed to result from an interaction of genetic and environmental factors, including the Epstein-Barr virus [EBV]. In an attempt to further clarify the pathogenesis of this disease, an evaluation of NPC occurring in racial/ethnic groups not considered susceptible to this disease could be informative. Methods. A white family with NPC occurring in three siblings was investigated and information was gleaned from literature on other reports of familial NPC in non-Chinese families. Results. In the family being investigated, another genetically determined disease, hemophilia, was identified. Radiation early in life was noted to be a possible risk factor for NPC in the proband. A review of familial NPC in the white population revealed that in contrast to sporadic NPC, which is usually of the well-differentiated type, familial NPC usually is poorly differentiated. Conclusions. Familial NPC offers an important opportunity to investigate the etiology of this disease. With newer laboratory techniques to investigate pathogenetic mechanisms, detailed evaluations of non-Chinese NPC families may become increasingly important. RP LEVINE, PH (reprint author), NCI,ENVIRONM EPIDEMIOL PROGRAM,EXECUT PLAZA N,ROOM 434,BETHESDA,MD 20892, USA. NR 35 TC 33 Z9 34 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1992 VL 70 IS 5 BP 1024 EP 1029 DI 10.1002/1097-0142(19920901)70:5<1024::AID-CNCR2820700503>3.0.CO;2-4 PG 6 WC Oncology SC Oncology GA JK783 UT WOS:A1992JK78300002 PM 1515979 ER PT J AU KREGER, BE ANDERSON, KM SCHATZKIN, A SPLANSKY, GL AF KREGER, BE ANDERSON, KM SCHATZKIN, A SPLANSKY, GL TI SERUM-CHOLESTEROL LEVEL, BODY-MASS INDEX, AND THE RISK OF COLON CANCER - THE FRAMINGHAM-STUDY SO CANCER LA English DT Article DE CHOLESTEROL; LIPIDS; LOW-DENSITY LIPOPROTEIN; OBESITY; RISK FACTORS; COLON CANCER; EPIDEMIOLOGY ID CORONARY HEART-DISEASE; PHYSICAL-ACTIVITY; LIPOPROTEIN CHOLESTEROL; MORTALITY; MEN; COHORT; WOMEN; POPULATION; PROGRAM; TRENDS AB Background. Some studies have linked low serum cholesterol levels to increased risk of colon cancer, particularly in men. Results have been inconsistent, with preclinical disease frequently offered to explain any apparent association. Methods. The Framingham Study cohort of 5209 persons, initially 30-62 years of age and observed more than 30 years, was evaluated. Baseline data included lipoprotein fractions, total cholesterol levels, body mass index, alcohol intake, and cardiovascular risk variables such as cigarette smoking, hypertension, and glucose intolerance. Results. In this population, colon cancer in men is related inversely to serum cholesterol levels, even when the first 10 years of follow-up are eliminated to reduce the effect of preclinical disease. This effect is concentrated in the Svedberg 0-20 fraction, corresponding to low-density lipoprotein levels. Another finding only in men is the direct relation of body mass index to colon cancer incidence. Conclusions. Combined initial low serum cholesterol levels and obesity appear to indicate a four times greater risk for colon cancer in men as compared with people with average values of both variables. The reasons for these observations are unknown. C1 BOSTON UNIV,MED CTR,GEN INTERNAL MED SECT,BOSTON,MA 02218. BOSTON UNIV,MED CTR,PREVENT MED SECT,BOSTON,MA 02218. BOSTON UNIV,MED CTR,EVANS MEM DEPT CLIN RES,EPIDEMIOL SECT,BOSTON,MA 02218. NHLBI,FRAMINGHAM HEART STUDY,FRAMINGHAM,MA 01701. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [5 R01 CA39766-02]; NHLBI NIH HHS [N01-HC-38038] NR 40 TC 71 Z9 71 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1992 VL 70 IS 5 BP 1038 EP 1043 DI 10.1002/1097-0142(19920901)70:5<1038::AID-CNCR2820700505>3.0.CO;2-M PG 6 WC Oncology SC Oncology GA JK783 UT WOS:A1992JK78300004 PM 1515981 ER PT J AU HSIA, CC AXIOTIS, CA DIBISCEGLIE, AM TABOR, E AF HSIA, CC AXIOTIS, CA DIBISCEGLIE, AM TABOR, E TI TRANSFORMING GROWTH FACTOR-ALPHA IN HUMAN HEPATOCELLULAR-CARCINOMA AND COEXPRESSION WITH HEPATITIS-B SURFACE-ANTIGEN IN ADJACENT LIVER SO CANCER LA English DT Article DE CARCINOGENESIS; HEPATITIS-B SURFACE ANTIGEN; HEPATITIS-B VIRUS; HEPATOCELLULAR CARCINOMA; HEPATOCYTE; LIVER; TRANSFORMING GROWTH FACTOR-ALPHA ID VIRUS TRANSGENIC MICE; MESSENGER-RNA; HUMAN KERATINOCYTES; FACTOR RECEPTOR; MAMMARY-GLAND; TGF-ALPHA; CANCER; OVEREXPRESSION; INDUCTION; CELLS AB Background. Hepatitis B virus [HBV] infection is closely associated with the development of hepatocellular carcinoma [HCC] in many patients, but the mechanisms by which HBV contributes to HCC are not known. Transforming growth factor-alpha [TGF-alpha], a regulator of growth and regeneration in rat liver that can be found in high levels in some human cancers, theoretically could play such an intermediate role in the development of HCC. Methods. The expression of TGF-alpha and its relation to the HBV antigens were evaluated in human HCC and adjacent nontumorous livers from 33 patients from the United States and China using immunoperoxidase staining of paraffin-embedded sections. Results. TGF-alpha was detected in HCC from 27 of 33 [82%] patients; the frequencies were similar in patients from the United States and China. TGF-alpha was detected in HCC more frequently in patients whose adjacent nontumorous livers had detectable hepatitis B surface antigen [HBsAg] and/or hepatitis B core antigen [HBcAg] than in those whose adjacent livers lacked HBsAg and HBcAg. Detection of TGF-alpha was not affected by tumor size, histologic type, or grade. TGF-alpha was detected in adjacent nontumorous livers from 31 of 33 patients [94%]. Coexpression at a high intensity of TGF-alpha and HBsAg in the same hepatocytes could be demonstrated by specific staining of consecutively cut sections for 17 of 33 patients [52%]. Conclusions. TGF-alpha is expressed at a high level in 82% of human HCC Localization of HBsAg within the same hepatocytes as TGF-alpha suggests a possible interaction between HBV and TGF-alpha during hepatocarcinogenesis in humans. Stimulation of TGF-alpha expression could be part of a chain of events by which HBV contributes to the development of HCC in some patients. C1 NCI,BIOL CARCINOGENESIS PROGRAM,BETHESDA,MD 20892. NIDDKD,LIVER DIS SECT,BETHESDA,MD. WARREN GRANT MAGNUSON CLIN CTR,OFF DIRECTOR,BETHESDA,MD. NR 26 TC 62 Z9 62 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1992 VL 70 IS 5 BP 1049 EP 1056 DI 10.1002/1097-0142(19920901)70:5<1049::AID-CNCR2820700507>3.0.CO;2-C PG 8 WC Oncology SC Oncology GA JK783 UT WOS:A1992JK78300006 PM 1325266 ER PT J AU GREENWALD, P AF GREENWALD, P TI COLON CANCER OVERVIEW SO CANCER LA English DT Article; Proceedings Paper CT NATIONAL CONF ON COLORECTAL CANCER CY MAR 20-22, 1991 CL NEW ORLEANS, LA SP AMER CANC SOC DE INCIDENCE AND MORTALITY; DIETARY FIBER; DIETARY FAT; CLINICAL DIETARY STUDIES; NCI DIETARY GUIDANCE; CHEMOPREVENTION; EARLY DETECTION AND SCREENING ID EPITHELIAL-CELL PROLIFERATION; DIETARY FIBER; ORNITHINE DECARBOXYLASE; COLORECTAL CANCERS; FATTY-ACIDS; F344 RATS; CARCINOGENESIS; AZOXYMETHANE; CHEMOPREVENTION; EPIDEMIOLOGY AB The scope of current prevention research support by the National Cancer Institute includes the clinical assessment of dietary modifications and cancer screening trials, epidemiologic studies, development of new chemopreventive therapies, and the use of advanced molecular biologic technologies to probe the genetic determinants of colorectal adenomas. Colorectal cancer frequently has been associated with high-fat low-fiber diets in epidemiologic and experimental studies. A recently initiated Phase III Dietary Intervention Study of Recurrence of Large Bowel Adenomatous Polyps will investigate the potential benefits of a low-fat high-fiber fruit-and-vegetable-enriched eating pattern to decrease the polyp recurrence rate. The Chemoprevention Program currently is supporting four Phase III controlled clinical intervention trials investigating the cancer-inhibiting effects on colorectal cancer of beta-carotene, piroxicam, calcium, and calcium plus fiber in persons with previous adenomas. A proposed early detection trial will screen for colorectal, prostate, lung, and ovarian cancers. A comparison of incidence and mortality trends indicates progress in colorectal cancer detection and therapy. RP GREENWALD, P (reprint author), NCI,DIV CANC PREVENT & CONTROL,BLDG 31,ROOM 10A52,BETHESDA,MD 20892, USA. NR 52 TC 89 Z9 92 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1992 VL 70 IS 5 SU S BP 1206 EP 1215 DI 10.1002/1097-0142(19920901)70:3+<1206::AID-CNCR2820701504>3.0.CO;2-J PG 10 WC Oncology SC Oncology GA JL193 UT WOS:A1992JL19300002 PM 1511368 ER PT J AU DINSE, GE HOEL, DG AF DINSE, GE HOEL, DG TI EXPLORING TIME TRENDS IN CANCER INCIDENCE SO CANCER CAUSES & CONTROL LA English DT Article DE BREAST CANCER; CANCER INCIDENCE; CANCER TRENDS; INTESTINAL CANCER; LUNG CANCER; PROSTATE CANCER; SEER PROGRAM; STOMACH CANCER; USA AB We examined incidence time-trends for lung, stomach, intestinal, prostate, and breast cancer among Whites diagnosed in the United States between 1973 and 1987. For each sex and five-year age group, we modeled cancer incidence as a log-linear function of diagnosis-year to permit extrapolation over time and simple summarization of trends. Comparisons with nonparametric estimates show that, except for breast cancer, the model performs well. Plots of the annual percent change in incidence cf age illustrate the way in which time trends depend on age. Between 1973 and 1987, stomach cancer incidence decreased by about two percent per year. The annual change in lung cancer incidence progressed from a two to three percent decrease in persons under age 40 to an increase of two percent in men and eight percent in women by age 80. Intestinal cancer incidence decreased annually by as much as three percent in persons under age 50, remained constant in women aged 50 to 74, and otherwise increased about one percent per year. The annual increase in prostate cancer incidence declined from about six percent in men under age 40 to about two percent in men over age 80. After a surge in female breast-cancer diagnoses in 1974, the annual increase in incidence between 1980 and 1987 stabilized at four to six percent. RP DINSE, GE (reprint author), NIEHS,STAT & BIOMATH BRANCH,B3-02,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 10 Z9 11 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1992 VL 3 IS 5 BP 409 EP 417 DI 10.1007/BF00051353 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JL169 UT WOS:A1992JL16900002 PM 1525321 ER PT J AU POTTERN, LM HEINEMAN, EF OLSEN, JH RAFFN, E BLAIR, A AF POTTERN, LM HEINEMAN, EF OLSEN, JH RAFFN, E BLAIR, A TI MULTIPLE-MYELOMA AMONG DANISH WOMEN - EMPLOYMENT HISTORY AND WORKPLACE EXPOSURES SO CANCER CAUSES & CONTROL LA English DT Article DE AGRICULTURE; CASE-CONTROL STUDY; DENMARK; FEMALES; INDUSTRY; MULTIPLE MYELOMA; OCCUPATION; TEXTILES AB To investigate the role of employment history and workplace exposures as risk factors for multiple myeloma among women, a population-based case-control study using the Danish Cancer Registry data linkage system was conducted. All cases of myeloma diagnosed in Danish women between 1970 and 1984 (1,010 cases) and 4,040 age-matched women alive at the time of case-diagnosis were identified. Industrial histories from 1964 forward were obtained from the nationwide Pension Fund for 363 cases and 1,517 controls, and the most recent occupation on the tax record was available for 607 cases and 2,596 controls. Using industry/occupational-code combinations for the cases and controls who had industry employment, Danish industrial hygienists assessed the likelihood of exposure to 47 workplace substances. An increased myeloma risk (odds ratio [OR] = 1.2, 95 percent confidence interval [CI] = 1.0-1.5) was seen for women not in the Pension Fund, but who had an occupational title coded as 'Mrs/homemaker.' Nonsignificantly elevated risks of 1.3 or greater were observed for employment in: production of agricultural products; orchards/nurseries; spinning/weaving; other textile and plastics manufacturing; hotel, entertainment, and social services industries. Elevated, but nonsignificant risks were observed for possible and probable exposure to exhaust fumes, formaldehyde, wood dust, animals or animal products, and pesticides. The strongest association with myeloma was employment in the agricultural industry (OR = 1.5, CI = 0.8-2.8), however, the number of women who worked on family farms was unknown and could not be included in this risk estimate. RP POTTERN, LM (reprint author), NCI,OCCUPAT STUDIES SECT,ENVIRONM EPIDEMIOL BRANCH,EPN 418,BETHESDA,MD 20892, USA. NR 0 TC 34 Z9 34 U1 1 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1992 VL 3 IS 5 BP 427 EP 432 DI 10.1007/BF00051355 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JL169 UT WOS:A1992JL16900004 PM 1525323 ER PT J AU DOODY, MM LINET, MS GLASS, AG FRIEDMAN, GD POTTERN, LM BOICE, JD FRAUMENI, JF AF DOODY, MM LINET, MS GLASS, AG FRIEDMAN, GD POTTERN, LM BOICE, JD FRAUMENI, JF TI LEUKEMIA, LYMPHOMA, AND MULTIPLE-MYELOMA FOLLOWING SELECTED MEDICAL CONDITIONS SO CANCER CAUSES & CONTROL LA English DT Article DE ALLERGY; AUTOIMMUNE DISEASES; EPIDEMIOLOGY; HEALTH MAINTENANCE ORGANIZATIONS; INFECTIOUS DISEASES; LEUKEMIA; LYMPHOMA; MULTIPLE MYELOMA; MUSCULOSKELETAL DISEASES; USA AB The role of selected prior medical conditions in the etiology of hematopoietic malignancies was examined in a case-control study of members of two regional branches of the Kaiser Permanente Medical Care Program (USA). Past history of chronic infectious, autoimmune, allergic, and musculoskeletal disorders was abstracted from medical records for leukemia (n = 299), non-Hodgkin's lymphoma (NHL, n = 1 00), and multiple myeloma (n = 175) cases and matched controls (n = 787). Little difference was found between cases and controls for most of the chronic conditions evaluated, including sinusitis, carbuncles, urinary tract infections, pelvic infections, herpes zoster, asthma, rheumatoid arthritis, psoriasis, bursitis, and gout. Only three statistically significant elevated risks were found, i.e., with combined disc disease myeloma among patients with prior eczema and disk and other musculoskeletal conditions, and NHL following tuberculosis. Only two of these associations showed consistent patterns by sex and geographic region (myeloma with eczema and with musculoskeletal conditions). While prior history of eczema and musculoskeletal conditions may slightly increase risk of myeloma, this study provided little if any support for an association of chronic infectious, autoimmune, allergic, and musculoskeletal conditions with subsequent occurrence of the leukemias or NHL. Additionally, these data did not support a role for chronic antigenic stimulation, as defined in previous epidemiologic studies, in the etiology of hematopoietic malignancies. RP DOODY, MM (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 408,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-01047, N01-CP-01054, N01-CP-11009] NR 0 TC 77 Z9 79 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1992 VL 3 IS 5 BP 449 EP 456 DI 10.1007/BF00051358 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JL169 UT WOS:A1992JL16900007 PM 1525326 ER PT J AU ZHENG, W BLOT, WJ SHU, XO DIAMOND, EL GAO, YT JI, BT FRAUMENI, JF AF ZHENG, W BLOT, WJ SHU, XO DIAMOND, EL GAO, YT JI, BT FRAUMENI, JF TI RISK-FACTORS FOR ORAL AND PHARYNGEAL CANCER IN SHANGHAI, WITH EMPHASIS ON DIET SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID REPUBLIC-OF-CHINA; NASOPHARYNGEAL CARCINOMA; SALTED FISH; CONSUMPTION; FOODS AB A population-based case-control study of oral and pharyngeal cancer was conducted in Shanghai, China, from 1988 to 1990, in which 204 (115 male, 89 female) incident cases and 414 (269 male, 145 female) controls were interviewed. Cigarette smoking and alcohol consumption, as well as occupational exposures to asbestos and to petroleum products and the use of kerosene stoves in cooking, were associated with increased risk of oral and pharyngeal cancer. In addition, more cases than controls reported having chronic oral diseases and false teeth. Dietary intakes of 42 major foods and selected salt-preserved or deep-fried foods during the past 10 years, ignoring any recent changes, were measured by a structured quantitative food questionnaire. After adjusting for known etiological factors, risks decreased with increasing intake of fruits, particularly oranges and tangerines, and some vegetables, including dark yellow vegetables and Chinese white radish. Men in the highest tertile of intake of these fruits and vegetables had about 30-50% the risk of those in the lowest tertile, with a less pronounced effect among women. A new finding was an excess risk associated with high consumption of salt-preserved meat and fish. The findings from this study provide further evidence that dietary factors play an important role in the development of oral and pharyngeal cancer. C1 SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. RP ZHENG, W (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 431,BETHESDA,MD 20892, USA. NR 36 TC 75 Z9 76 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP-OCT PY 1992 VL 1 IS 6 BP 441 EP 448 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JP118 UT WOS:A1992JP11800004 PM 1302555 ER PT J AU MARGULIES, IMK HOYHTYA, M EVANS, C STRACKE, ML LIOTTA, LA STETLERSTEVENSON, WG AF MARGULIES, IMK HOYHTYA, M EVANS, C STRACKE, ML LIOTTA, LA STETLERSTEVENSON, WG TI URINARY TYPE-IV COLLAGENASE - ELEVATED LEVELS ARE ASSOCIATED WITH BLADDER TRANSITIONAL CELL-CARCINOMA SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TISSUE INHIBITOR; FLOW-CYTOMETRY; CANCER; EXPRESSION; MARKER; TIMP-2; IDENTIFICATION; INVASION; LINES AB Accumulating experimental evidence has linked the overproduction of extracellular matrix-degrading metalloproteinases with tumor cell invasion. In the present study one member of the metalloproteinase family, type IV collagenase (M(r) 72,000 gelatinase), is shown to be elevated in the urine of patients with transitional cell carcinoma of the bladder. The form of the enzyme in the urine was studied by three independent methods: enzyme-linked immunosorbent assay, Western immunoblotting; and gelatin zymography. Immunoblotting revealed that the enzyme was present as a series of fragments, each retaining the amino terminus of the mature proenzyme. A prominent M(r) 43,000 fragment was associated with the transitional cell carcinoma cases. Zymography demonstrated that multiple enzyme species with gelatinase activity were present in urine and that high-molecular-weight bands of substrate lysis corresponded to complexes between type IV collagenase and tissue inhibitor of metalloproteinases 2. The total amount of type IV collagenase antigen was significantly elevated in the urine of 37 transitional cell carcinoma patients (range, 0-1081 ng/ml; mean, 318.4 +/- 147.3) compared to 19 normal controls (P less-than-or-equal-to 0.004) and 17 inflammatory disease controls (P less-than-or-equal-to 0.011). Immunohistochemical staining of bladder tumor biopsies verified that the transitional cell carcinoma cells were producing the M(r) 72,000 enzyme. Thus, M(r) 72,000 type IV collagenase, which is present in the urine in many forms including fragments and complexes with inhibitors, may be a useful marker for bladder cancer diagnosis or prognosis. C1 MOLEC ONCOL INC,GAITHERSBURG,MD 20878. UNIV CALIF SAN FRANCISCO,DEPT UROL,SAN FRANCISCO,CA 94143. RP MARGULIES, IMK (reprint author), NCI,PATHOL LAB,BLDG 10,ROOM 2A33,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 25 TC 61 Z9 61 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP-OCT PY 1992 VL 1 IS 6 BP 467 EP 474 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JP118 UT WOS:A1992JP11800008 PM 1302559 ER PT J AU ZUCKER, S LYSIK, RM ZARRABI, MH STETLERSTEVENSON, W LIOTTA, LA BIRKEDALHANSEN, H MANN, W FURIE, M AF ZUCKER, S LYSIK, RM ZARRABI, MH STETLERSTEVENSON, W LIOTTA, LA BIRKEDALHANSEN, H MANN, W FURIE, M TI TYPE-IV COLLAGENASE GELATINASE (MMP-2) IS NOT INCREASED IN PLASMA OF PATIENTS WITH CANCER SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; METASTATIC TUMOR-CELLS; ENDOTHELIAL-CELLS; METALLOPROTEINASES; EXPRESSION; SECRETION; PURIFICATION; PHENOTYPE; ENZYME; GENES AB We have developed a sensitive and specific sandwich-type enzyme-linked immunosorbent assay to detect M(r) 72,000 type IV collagenase [matrix metalloproteinase 2 (MMP-2)] in human plasma. As a result of the linkage between MMP-2 production by cancer cells and the metastatic phenotype, we undertook this study to compare plasma MMP-2 levels in healthy individuals, patients with various types of cancer, and hospitalized patients with chronic diseases other than cancer. The results demonstrate that MMP-2 levels are not increased in cancer patients regardless of the extent of disseminated malignancy. In an effort to explain this data, we compared MMP-2 secretion by human umbilical vein endothelial cells and lung cancer cells passaged as cell lines. Endothelial cells secreted higher levels of MMP-2 than did lung cancer cells propagated in vitro. We propose that blood vessel lining cells make a sizable contribution to plasma levels of MMP-2 and may thereby obfuscate the detection of increased levels of MMP-2 originating from extravascular sources such as solid tumors. C1 DEPT VET AFFAIRS MED CTR,DEPT MED,NORTHPORT,NY 11768. SUNY STONY BROOK,DEPT MED,STONY BROOK,NY 11794. SUNY STONY BROOK,DEPT OBSTET GYNECOL,STONY BROOK,NY 11794. SUNY STONY BROOK,DEPT PATHOL,STONY BROOK,NY 11794. NCI,PATHOL LAB,TUMOR INFAS & METASTASIS SECT,BETHESDA,MD 20892. UNIV ALABAMA,ORAL BIOL RES CTR,DEPT ORAL BIOL,BIRMINGHAM,AL 35294. RP ZUCKER, S (reprint author), DEPT VET AFFAIRS MED CTR,DEPT RES,MAIL CODE 151,NORTHPORT,NY 11768, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 23 TC 35 Z9 35 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP-OCT PY 1992 VL 1 IS 6 BP 475 EP 479 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JP118 UT WOS:A1992JP11800009 PM 1302560 ER PT J AU WESTON, A PERRIN, LS FORRESTER, K HOOVER, RN TRUMP, BF HARRIS, CC CAPORASO, NE AF WESTON, A PERRIN, LS FORRESTER, K HOOVER, RN TRUMP, BF HARRIS, CC CAPORASO, NE TI ALLELIC FREQUENCY OF A P53 POLYMORPHISM IN HUMAN LUNG-CANCER SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENE-MUTATIONS; CARCINOMAS; DELETIONS; OCCUR; LOCUS AB p53 is a tumor suppressor gene that is mutated in diverse tumor types. Here we report the frequencies of common polymorphic variants at codon 72 of the p53 gene in germline DNA of lung cancer cases and controls as determined by a polymerase chain reaction strategy. The observed allelic distribution was found to be significantly different between African-Americans and Caucasians in this U.S. population. The frequency of polymorphic variants was similar in lung cancer cases and controls after adjustment for race. However, among lung cancer patients the proline variant at codon 72 was in excess in adenocarcinoma patients by comparison with other histologies. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. RP WESTON, A (reprint author), NCI,MOLEC EPIDEMIOL SECT,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C16,BETHESDA,MD 20892, USA. NR 24 TC 83 Z9 83 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP-OCT PY 1992 VL 1 IS 6 BP 481 EP 483 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JP118 UT WOS:A1992JP11800010 PM 1302561 ER PT J AU AMOS, CI CAPORASO, NE WESTON, A AF AMOS, CI CAPORASO, NE WESTON, A TI HOST FACTORS IN LUNG-CANCER RISK - A REVIEW OF INTERDISCIPLINARY STUDIES SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID ARYL-HYDROCARBON HYDROXYLASE; DEBRISOQUINE METABOLIC PHENOTYPE; OBSTRUCTIVE PULMONARY-DISEASE; CARCINOGEN-HEMOGLOBIN ADDUCTS; POLYCYCLIC AROMATIC-COMPOUNDS; FRAGMENT-LENGTH-POLYMORPHISM; SISTER CHROMATID EXCHANGE; ALVEOLAR CELL-CARCINOMA; ACETYLATION PHENOTYPE; CIGARETTE-SMOKING AB Host-specific factors influence risk for lung cancer. A few case-control and family studies of lung cancer susceptibility allowed for known lung cancer carcinogens and showed strong familial clustering with some evidence for a codominantly acting major gene. Cytochrome P-450 enzymes (e.g., CYP1A1) activate many carcinogens in tobacco smoke but have shown inconsistent associations with risk for lung cancer. Case-control studies that assess the effects of CYPIID6 on lung cancer risk have consistently shown a mildly decreased risk for lung cancer among poor metabolizers. Cell surface markers have shown little relation to risk for lung cancer. Studies involving DNA or hemoglobin adducts, sister chromatid exchange, or oncogene activation only indirectly measure host-specific risk, and these assays have suffered from poor reproducibility and high cost. We describe epidemiological designs to assess specific genetic factors that may alter lung cancer risk. C1 INT AGCY RES CANC,DIV BIOSTAT RES & INFORMAT,F-69372 LYON,FRANCE. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RP AMOS, CI (reprint author), NIAMSK,GENET STUDIES SECT,SKIN BIOL LAB,BLDG 6,ROOM 429,BETHESDA,MD 20892, USA. NR 121 TC 80 Z9 80 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP-OCT PY 1992 VL 1 IS 6 BP 505 EP 513 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JP118 UT WOS:A1992JP11800014 PM 1302563 ER PT J AU LEVINE, PH HOOVER, R AF LEVINE, PH HOOVER, R TI THE EMERGING EPIDEMIC OF NON-HODGKINS-LYMPHOMA - CURRENT KNOWLEDGE REGARDING ETIOLOGIC FACTORS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material RP LEVINE, PH (reprint author), NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 19 Z9 19 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP-OCT PY 1992 VL 1 IS 6 BP 515 EP 517 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JP118 UT WOS:A1992JP11800015 PM 1363833 ER PT J AU IWAMOTO, K OBRAMS, GI SCHOTTENFELD, D AF IWAMOTO, K OBRAMS, GI SCHOTTENFELD, D TI THE ROLE OF BIOLOGICAL MARKERS IN EPIDEMIOLOGIC RESEARCH - FUTURE-DIRECTIONS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT EPIDEMIOL,ANN ARBOR,MI 48103. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP-OCT PY 1992 VL 1 IS 6 BP 519 EP 522 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JP118 UT WOS:A1992JP11800016 PM 1363834 ER PT J AU HIGINBOTHAM, KG RICE, JM DIWAN, BA KASPRZAK, KS REED, CD PERANTONI, AO AF HIGINBOTHAM, KG RICE, JM DIWAN, BA KASPRZAK, KS REED, CD PERANTONI, AO TI GGT TO GTT TRANSVERSIONS IN CODON-12 OF THE K-RAS ONCOGENE IN RAT RENAL SARCOMAS INDUCED WITH NICKEL SUBSULFIDE OR NICKEL SUBSULFIDE IRON ARE CONSISTENT WITH OXIDATIVE DAMAGE TO DNA SO CANCER RESEARCH LA English DT Article ID F344 RATS; TUMORS; MUTAGENESIS; CANCERS; SITE; CARCINOGENESIS; AUTOXIDATION; INJECTION; INSERTION; INVITRO AB Nickel is a toxic, mutagenic, and carcinogenic metal of significant occupational and environmental concern. Although several cellular targets of nickel have been identified, considerable evidence suggests that it can act indirectly upon DNA by inducing the formation of oxidized purines or pyrimidines that constitute promutagenic lesions. In this study, we examined nickel subsulfide (Ni3S2)- or Ni3S2/iron-induced renal sarcomas in F344 rats for the presence of transforming mutations in the K-ras oncogene. Selective oligonucleotide hybridization analysis of K-ras gene sequences amplified by polymerase chain reaction revealed that 1 of 12 primary tumors induced with Ni3S2 and 7 of 9 primary tumors induced with Ni3S2/iron contained exclusively GGT to GTT activating mutations in codon 12. These mutations are consistent with the known ability of nickel, in the presence of an oxidizing agent, to catalyze formation of 8-hydroxydeoxyguanosine, which in turn promotes misincorporation of dATP opposite the oxidized guanine residue. The presence of GGT to GTT transversions was confirmed by direct sequencing of the polymerase chain reaction products. Sequencing also revealed that there were no transforming mutations in codons 13 or 59-61. Additionally, a direct correlation between shortened tumor latency and the presence of activating ras mutations was noted. These results show that, in rat kidney, Ni3S2 can induce transforming mutations that are consistent with the ability of nickel to produce oxidative lesions and that iron, which exacerbates the extent of cellular oxidative damage, can enhance the frequency of these transforming mutations. C1 NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. DYNCORP,PROGRAM RES INC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 35 TC 76 Z9 78 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1992 VL 52 IS 17 BP 4747 EP 4751 PG 5 WC Oncology SC Oncology GA JK679 UT WOS:A1992JK67900028 PM 1511440 ER PT J AU MALKINSON, AM SIEGEL, D FORREST, GL GAZDAR, AF OIE, HK CHAN, DC BUNN, PA MABRY, M DYKES, DJ HARRISON, SD ROSS, D AF MALKINSON, AM SIEGEL, D FORREST, GL GAZDAR, AF OIE, HK CHAN, DC BUNN, PA MABRY, M DYKES, DJ HARRISON, SD ROSS, D TI ELEVATED DT-DIAPHORASE ACTIVITY AND MESSENGER-RNA CONTENT IN HUMAN NON-SMALL-CELL LUNG-CARCINOMA - RELATIONSHIP TO THE RESPONSE OF LUNG-TUMOR XENOGRAFTS TO MITOMYCIN-C SO CANCER RESEARCH LA English DT Article ID BIOREDUCTIVE ALKYLATING-AGENTS; INDUCED DNA DAMAGE; NAD(P)H-QUINONE OXIDOREDUCTASE; HYPOXIC CONDITIONS; MOUSE LUNG; CANCER; REDUCTASE; LINES; GENE; METABOLISM AB The enzyme DT-diaphorase (DTD; NAD(P)H:quinone oxidoreductase, EC 1.6.99.2), is an obligate two electron reductase which catalyzes reduction of a broad range of substrates, including quinones. We report here variations in DTD concentrations among different classes of lung tumors known also to vary in their responsiveness to cytotoxic agents. Small cell lung carcinomas (SCLCs) and cell lines derived from them have the low DTD activities and mRNA content characteristic of normal human lung, whereas non-small cell lung carcinomas (NSCLCs) have greatly elevated levels. DTD activity was increased up to 80-fold in NSCLC tumors relative to normal lung and 20-35-fold in NSCLC relative to SCLC cell lines. Increased DTD activity appeared to be a function of the NSCLC phenotype rather than a result of derivation from a cell type rich in DTD, since all histological classes of NSCLC showed this phenotype. In addition, where transfection of SCLC cell lines with the v-Ha-ras protooncogene caused a transition to a NSCLC phenotype, DTD activity was also elevated. Neuroendocrine-positive cells (SCLC, carcinoids, and a few NSCLC lines) typically had far lower DTD activities than did cell lines which lacked neuroendocrine markers (most NSCLC cells and mesotheliomas). High DTD activity may be exploited in the design of drugs which undergo bioreductive activation by this enzyme. Consistent with this, xenografts derived from NSCLC cell lines with high DTD that were grown in athymic nude mice were more susceptible to the antitumor quinone, mitomycin C, than were xenografts derived from SCLC cells containing low DTD. These data provide a mechanistic basis for the rational design of more effective bioreductive antitumor agents for use against NSCLC. C1 UNIV COLORADO,MOLEC TOXICOL & ENVIRONM HLTH SCI,BOULDER,CO 80309. UNIV COLORADO,SCH PHARM,BOULDER,CO 80309. CITY HOPE NATL MED CTR,BECKMAN RES INT,DUARTE,CA 91010. NCI,USN,MED ONCOL BRANCH,BETHESDA,MD 20814. UNIV COLORADO,SCH MED,DIV MED ONCOL,DENVER,CO 80262. UNIV COLORADO,SCH MED,CTR CANC,DENVER,CO 80262. JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD 21205. SO RES INST,BIRMINGHAM,AL 35255. FU NCI NIH HHS [N01-CM-97553, R01 CA 51210]; NIEHS NIH HHS [R01 ES 02370] NR 46 TC 155 Z9 156 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1992 VL 52 IS 17 BP 4752 EP 4757 PG 6 WC Oncology SC Oncology GA JK679 UT WOS:A1992JK67900029 PM 1324793 ER PT J AU HARRIS, CC HIROHASHI, S ITO, N PITOT, HC SUGIMURA, T TERADA, M YOKOTA, J AF HARRIS, CC HIROHASHI, S ITO, N PITOT, HC SUGIMURA, T TERADA, M YOKOTA, J TI MULTISTAGE CARCINOGENESIS - THE 22ND INTERNATIONAL-SYMPOSIUM OF THE PRINCESS-TAKAMATSU-CANCER-RESEARCH-FUND SO CANCER RESEARCH LA English DT Editorial Material C1 NATL CANC CTR,RES INST,TOKYO 104,JAPAN. NAGOYA CITY UNIV,SCH MED,DEPT PATHOL 1,MIZUHO KU,NAGOYA,AICHI 467,JAPAN. UNIV WISCONSIN,MCARDLE LAB CANC RES,MADISON,WI 53706. NAGOYA CITY UNIV,RES INST,DIV GENET,NAGOYA,AICHI 467,JAPAN. RP HARRIS, CC (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1992 VL 52 IS 17 BP 4837 EP 4840 PG 4 WC Oncology SC Oncology GA JK679 UT WOS:A1992JK67900044 PM 1511448 ER PT J AU JANG, JJ WEGHORST, CM HENNEMAN, JR DEVOR, DE WARD, JM AF JANG, JJ WEGHORST, CM HENNEMAN, JR DEVOR, DE WARD, JM TI PROGRESSIVE ATYPIA IN SPONTANEOUS AND N-NITROSODIETHYLAMINE-INDUCED HEPATOCELLULAR ADENOMAS OF C3H/HENCR MICE SO CARCINOGENESIS LA English DT Article ID MOUSE-LIVER TUMORS; MALIGNANT CONVERSION; CARCINOMA SEQUENCE; RAS ONCOGENE; SKIN TUMORS; CARCINOGENESIS; DIETHYLNITROSAMINE; CANCER; HEPATOCARCINOGENESIS; PROMOTION AB The progression of hepatocellular adenomas to carcinomas has been less well documented in mice than in rats. We studied progression of spontaneous and chemically induced hepatocellular adenomas in male C3H/HeNCr mice by image analysis. Spontaneous lesions in 15, 18 and 21 month old untreated male C3H/HeNCr mice and experimentally induced lesions were examined. Experimental group 1 received a single i.p. injection of N-nitrosodiethylamine (DEN) (5 mg/kg body wt) at 15 days of age. Groups 2 and 3 were injected a second time with DEN at 15 or 20 weeks of age (75 mg/kg body wt), with interim sacrifices at 11, 16 and 34 weeks after the second DEN injection. Atypia in adenomas were classified into four grades according to cell size, tinctorial changes, cellular pleomorphism and trabecular pattern. At earlier stages of the neoplastic process (11 or 16 weeks after the second DEN dose), most adenomas were well-differentiated lesions with no atypia or focal grade 1 or 2 atypia. At later stages (34 weeks after the second DEN dose), a large proportion of hepatocellular tumors were classified as adenoma with grade 3 atypia or carcinoma. The proportion of carcinomas in mice treated with a second dose of DEN at 20 weeks of age was significantly higher than in mice treated with a single dose of DEN or in mice given a second dose of DEN at 15 weeks. A positive correlation was found between increase in the size of lesions and increased atypia in both spontaneous and DEN-induced lesions and with age for spontaneous tumors. These results support the hypothesis that mouse hepatocellular adenomas are truly neoplastic lesions in different stages of progression toward malignancy. C1 NCI,COMPARAT CARCINOGENESIS LAB,TUMOR PATHOL & PATHOGENESIS SECT,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI Jang, JaJune/F-6647-2011 FU NCI NIH HHS [N01-CO-74102] NR 36 TC 15 Z9 15 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1992 VL 13 IS 9 BP 1541 EP 1547 PG 7 WC Oncology SC Oncology GA JP547 UT WOS:A1992JP54700009 PM 1394837 ER PT J AU YOU, M WANG, Y LINEEN, AM GUNNING, WT STONER, GD ANDERSON, MW AF YOU, M WANG, Y LINEEN, AM GUNNING, WT STONER, GD ANDERSON, MW TI MUTAGENESIS OF THE K-RAS PROTOONCOGENE IN MOUSE LUNG-TUMORS INDUCED BY N-ETHYL-N-NITROSOUREA OR N-NITROSODIETHYLAMINE SO CARCINOGENESIS LA English DT Article ID SITE-SPECIFIC MUTAGENESIS; ESCHERICHIA-COLI; LIVER-TUMORS; CHEMICAL CARCINOGENESIS; MUTATIONAL ACTIVATION; CONTINUOUS EXPOSURE; B6C3F1 MOUSE; ONCOGENES; REPAIR; RATS AB The role of ras gene activation in the development of lung tumors induced by N-ethyl-N-nitrosourea (ENU) and N-nitrosodiethylamine (DEN) was evaluated in the A/J mouse, a strain susceptible to chemically induced lung tumors. DNAs isolated from both ENU- and DEN-induced lung tumors were screened for activating mutations in the K-ras gene by utilizing the polymerase chain reaction (PCR) and direct sequence analysis. Mutations in the K-ras gene were detected in 11 of 11 ENU-induced tumors and 23 of 28 DEN-induced tumors. In ENU-induced tumors, there were three GC --> AT transitions in the second base of codon 12, and seven AT --> GC transitions and one AT --> TA transversion in the second base of codon 61. A similar spectrum of K-ras mutations was observed in DEN-induced lung tumors: five GC --> AT transitions and two GC --> TA transversions in the second base of codon 12, and sixteen AT --> GC transitions at the second base of codon 61. Ninety-one percent (31/34) of the observed mutations are consistent with the formation of the promutagenic O4-ethylthymine and O6-ethylguanine adducts in DNA. Therefore, lung tumors from the A/J mouse induced by DEN and ENU could be initiated by the interaction of reactive metabolites with specific sites in the K-ras gene. This is the first clear example of activation of the K-ras gene by ethylating agents in a rodent lung tumor system. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP YOU, M (reprint author), MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43699, USA. RI Gunning, William/E-4681-2010 NR 39 TC 52 Z9 52 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1992 VL 13 IS 9 BP 1583 EP 1586 DI 10.1093/carcin/13.9.1583 PG 4 WC Oncology SC Oncology GA JP547 UT WOS:A1992JP54700015 PM 1394843 ER PT J AU SABOURIN, PJ BURKA, LT BECHTOLD, WE DAHL, AR HOOVER, MD CHANG, IY HENDERSON, RF AF SABOURIN, PJ BURKA, LT BECHTOLD, WE DAHL, AR HOOVER, MD CHANG, IY HENDERSON, RF TI SPECIES-DIFFERENCES IN URINARY BUTADIENE METABOLITES - IDENTIFICATION OF 1,2-DIHYDROXY-4-(N-ACETYLCYSTEINYL)BUTANE, A NOVEL METABOLITE OF BUTADIENE SO CARCINOGENESIS LA English DT Article ID RUBBER WORKERS; LYMPHATIC MALIGNANCIES; INHALATION EXPOSURE; MORTALITY PATTERNS; 1,3-BUTADIENE; CARCINOGENICITY; INDUSTRY; RATS; MICE AB 1,3-Butadiene (BD) is used in the manufacture of styrene-BD and polybutadiene rubber. Differences seen in chronic toxicity studies in the susceptibility of B6C3F1 mice and Sprague - Dawley rats to BD raise the question of how to use the rodent toxicology data to predict the health risk of BD in humans. The purpose of this study was to determine if there are species differences in the metabolism of BD to urinary metabolites that might help to explain the differences in the toxicity of BD. The major urinary metabolites of BD in F344/N rats, Sprague-Dawley rats, B6C3F1 mice, Syrian hamsters, and cynomolgus monkeys were identified as 1,2-dihydroxy-4-(N-acetylcysteinyl)-butane (I) and the N-acetylcysteine conjugate of BD monoxide [1-hydroxy-2-(N-acetylcysteinyl)-3-butene] (II). These mercapturic acids are formed by addition of glutathione at either the double bond (I) or the epoxide (II) respectively. When exposed to approximately 8000 p.p.m. of BD for 2 h, the mice excreted 3 - 4 times as much metabolite II as I, the hamster and the rats produced approximately 1.5 times as much metabolite II as I, while the monkeys produced primarily metabolite I. The ratio of formation of metabolite I to the total formation of the two mercapturic acids correlated well with the known hepatic epoxide hydrolase activity in the different species. These data suggest that (i) the availability of the monoepoxide for conjugation with glutathione is highest in the mouse, followed by the hamster and the rat, and is lowest in the monkey; and (ii) the epoxide availability is inversely related to the hepatic activity of epoxide hydrolase, the enzyme that removes the epoxide by hydrolysis. The ratio of the two mercapturic acids in human urine following BD exposure may indicate the pathways of BD metabolism in humans and may aid in the determination of the most appropriate animal model for BD toxicity. C1 LOVELACE BIOMED & ENVIRONM RES INST,INHALAT TOXICOL RES INST,POB 5890,ALBUQUERQUE,NM 87185. NIEHS,RES TRIANGLE PK,NC 27709. RI Hoover, Mark/I-4201-2012 OI Hoover, Mark/0000-0002-8726-8127 NR 21 TC 62 Z9 64 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1992 VL 13 IS 9 BP 1633 EP 1638 DI 10.1093/carcin/13.9.1633 PG 6 WC Oncology SC Oncology GA JP547 UT WOS:A1992JP54700023 PM 1394848 ER PT J AU GABRIELSON, EW KUPPUSAMY, P POVEY, AC ZWEIER, JL HARRIS, CC AF GABRIELSON, EW KUPPUSAMY, P POVEY, AC ZWEIER, JL HARRIS, CC TI MEASUREMENT OF NEUTROPHIL ACTIVATION AND EPIDERMAL-CELL TOXICITY BY PALYTOXIN AND 12-O-TETRADECANOYLPHORBOL-13-ACETATE SO CARCINOGENESIS LA English DT Note ID BRONCHIAL EPITHELIAL-CELLS; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; PHORBOL MYRISTATE ACETATE; TUMOR PROMOTERS; DIFFERENTIATION; KERATINOCYTES; GROWTH; STIMULATION; TELEOCIDIN; METABOLISM AB Palytoxin is a human and mouse skin irritant and complete mouse skin tumor promoter that differs from the well-studied phorbol ester class of tumor promoters in many respects. In this study, we have found palytoxin to stimulate the production of superoxide by isolated human neutrophils using electron paramagnetic resonance (EPR) spectroscopy with the spin-trap DMPO. This stimulation of oxyradical production by palytoxin is relatively weak, however, when compared to that by 12-O-tetradecanoylphorbol-13-acetate (TPA). The maximal amount of oxyradicals produced by palytoxin-stimulated neutrophils is 10(-4) mumol/10(6) neutrophils, and this stimulation requires nanomolar concentrations of palytoxin, with half maximal stimulation at concentrations of approximately 30 nM. In contrast, the tumor promoter TPA causes human neutrophils to generate in excess of 10(-3) mumol oxyradicals/10(6) neutrophils with concentrations as low as 1 nM. Toxicity to cultured human epidermal cells was observed at very low concentrations of palytoxin, with 50% loss of colony-forming efficiency observed at approximately 3 x 10(-13) M. For TPA, 50% loss of colony-forming efficiency for cultured epidermal cells requires approximately 5 nM. Thus, although palytoxin stimulates superoxide production in isolated neutrophils, epidermal cells are sensitive at much lower concentrations and are likely to be the important target cell in vivo. This is in contrast to TPA, where neutrophils are stimulated at concentrations less than those required to produce pathological effects on epidermal cells, suggesting that neutrophils may be an important target cell for TPA in vivo. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CARDIOL,ELECTRON PARAMAGNET RESONANCE LABS,BALTIMORE,MD 21224. NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 25 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1992 VL 13 IS 9 BP 1671 EP 1674 DI 10.1093/carcin/13.9.1671 PG 4 WC Oncology SC Oncology GA JP547 UT WOS:A1992JP54700030 PM 1356652 ER PT J AU GOPAS, J ONO, M PRINCLER, G SMITH, MR TAINSKY, MA SIDDIQUI, MAQ WISHNIAK, O SEGAL, S KUWANO, M KUNG, HF AF GOPAS, J ONO, M PRINCLER, G SMITH, MR TAINSKY, MA SIDDIQUI, MAQ WISHNIAK, O SEGAL, S KUWANO, M KUNG, HF TI EGF RECEPTOR ACTIVITY AND MITOGENIC RESPONSE OF BALB/3T3 CELLS EXPRESSING RAS AND MYC ONCOGENES SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE RAS; MYC; AND EPIDERMAL GROWTH FACTOR RECEPTOR ID EPIDERMAL GROWTH-FACTOR; MAMMARY EPITHELIAL-CELLS; C-MYC; TRANSFORMATION; PROTEIN; ALPHA; RESPONSIVENESS; COOPERATION; REQUIRES; BINDING AB EGF receptors are found on the surface of most cells, usually with high and low binding affinities. To investigate functional relationships between EGF (EGF-like growth factors) and oncogenes we have characterized the expression of the epidermal growth factor receptor (EGFr) in H-Ras, v-Myc, and H-Ras-v-Myc transformed Balb/3T3 cells. H-Ras cells show a marked decrease in the number of EGFr molecules per cell compared to parental cells. v-Myc and H-Ras-v-Myc transformed cells express an intermediate level of receptors. The majority of the EGF receptors on the parental and oncogene transformed cells bind EGF with low affinity and this low affinity receptor is down-regulated by oncogene transformation. v-Myc expression, in the H-Ras-v-Myc transformed cells, abrogates the receptor down-regulation seen with H-Ras transformation. The mechanism of abrogation is not a result of a change in the p21-Ras concentration in the H-Ras-v-Myc transformed cells. In addition, the mitogenic response to EGF was examined. H-Ras and H-Ras-v-Myc transformed cells do not respond to EGF mitogenically. In contrast, EGF stimulates DNA synthesis in parental cells and v-Myc transfected cells; this result suggests that growth promoting signals from the EGF receptor may not be required in H-Ras transformed cells. C1 BEN GURION UNIV NEGEV,FAC HLTH SCI,DEPT MICROBIOL & IMMUNOL,IL-84105 BEER SHEVA,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. SUNY HLTH SCI CTR BROOKLYN,DEPT ANAT & CELL BIOL,BROOKLYN,NY 11203. OITA MED SCH,DEPT BIOCHEM,HASAMA,OITA 87955,JAPAN. PROGRAM RESOURCES INC DYNCORP,NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030. FU NCI NIH HHS [N01-CO-74102] NR 29 TC 14 Z9 14 U1 0 U2 0 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD SEP PY 1992 VL 38 IS 6 BP 605 EP 614 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV536 UT WOS:A1992KV53600005 PM 1303308 ER PT J AU PURI, RK FITZGERALD, D LELAND, P KOZAK, RW PASTAN, I AF PURI, RK FITZGERALD, D LELAND, P KOZAK, RW PASTAN, I TI INVITRO AND INVIVO SUPPRESSION OF INTERLEUKIN-2-ACTIVATED KILLER-CELL ACTIVITY BY CHIMERIC PROTEINS BETWEEN INTERLEUKIN-2 AND PSEUDOMONAS EXOTOXIN SO CELLULAR IMMUNOLOGY LA English DT Article ID TUMOR-CELLS; RECOMBINANT INTERLEUKIN-2; LYMPHOCYTES-T; IL-2-PE40; EXPRESSION; METASTASES; RECEPTORS; LYSIS; MICE C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RP PURI, RK (reprint author), NIH,US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892, USA. NR 20 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD SEP PY 1992 VL 143 IS 2 BP 324 EP 334 DI 10.1016/0008-8749(92)90029-O PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA JL406 UT WOS:A1992JL40600007 PM 1511480 ER PT J AU CANELLA, KA PELTONEN, K YAGI, H JERINA, DM DIPPLE, A AF CANELLA, KA PELTONEN, K YAGI, H JERINA, DM DIPPLE, A TI IDENTIFICATION OF INDIVIDUAL BENZO[C]PHENANTHRENE DIHYDRODIOL EPOXIDE-DNA ADDUCTS BY THE P-32 POSTLABELING ASSAY SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID 3,4-DIOL-1,2-EPOXIDES AB Purine deoxyribonucleoside 3'-phosphates were reacted separately with the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide. Products resulting from the cis and trans opening of the epoxide ring by the exocyclic amino groups of deoxyadenosine and deoxyguanosine 3'-phosphates were separated by high-pressure liquid chromatography and identified by comparison of the observed circular dichroism spectra with the known spectra for the corresponding nucleoside adducts. The 16 structurally identified benzo[c]phenanthrene-purine deoxyribonucleoside 3'-phosphate adducts were then separately postlabeled according to the Randerath method, and the positions of the individual bisphosphates were mapped by thin-layer chromatography. Chromatographic conditions were developed that allowed separation of the four adducts for 3 of the 4 dihydrodiol epoxide isomers. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP CANELLA, KA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CHEM CARCINOGENESES LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 15 TC 21 Z9 21 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP-OCT PY 1992 VL 5 IS 5 BP 685 EP 690 DI 10.1021/tx00029a015 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA JN551 UT WOS:A1992JN55100015 PM 1446010 ER PT J AU HARRIS, JW JONES, JP MARTIN, JL LAROSA, AC OLSON, MJ POHL, LR ANDERS, MW AF HARRIS, JW JONES, JP MARTIN, JL LAROSA, AC OLSON, MJ POHL, LR ANDERS, MW TI PENTAHALOETHANE-BASED CHLOROFLUOROCARBON SUBSTITUTES AND HALOTHANE - CORRELATION OF INVIVO HEPATIC PROTEIN TRIFLUOROACETYLATION AND URINARY TRIFLUOROACETIC-ACID EXCRETION WITH CALCULATED ENTHALPIES OF ACTIVATION SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID RAT-LIVER MICROSOMES; METABOLIC BASIS; ANTIBODIES; HEPATOTOXICITY; HYDROXYLATION; NEOANTIGENS; OXIDATION; ENFLURANE; PROGRESS; OZONE AB The hydrochlorofluorocarbons (HCFCs) 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) and 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124) and the hydrofluorocarbon (HFC) pentafluoroethane (HFC-125) are being developed as substitutes for chlorofluorocarbons that deplete stratospheric ozone. The structural similarity of these HCFCs and HFCs to halothane, which is hepatotoxic under certain circumstances, indicates that the metabolism and cellular interactions of HCFCs and HFCs must be explored. In a previous study [Harris et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 1407], similar patterns of trifluoroacetylated proteins (TFA-proteins) were detected by immunoblotting with anti-TFA-protein antibodies in livers of rats exposed to halothane or HCFC-123. The present study extends these results and demonstrates that in vivo TFA-protein formation resulting from a 6-h exposure to a 1 % atmosphere of these compounds follows the trend: halothane almost-equal-to HCFC-123 much greater than HCFC-124 > HFC-125. The calculated enthalpies of activation of halothane, HCFC-123, HCFC-124, and HFC-125 paralleled the observed rate of trifluoroacetic acid excretion in HCFC- or HFC-exposed rats. Exposure of rats to a range of HCFC- 123 concentrations indicated that TFA-protein formation was saturated at an exposure concentration between 0.01% and 0.1% HCFC-123. Deuteration of HCFC-123 decreased TFA-protein formation in vivo. Urinary trifluoroacetic acid excretion by treated rats correlated with the levels of TFA-proteins found after each of these treatments. No TFA-proteins were detected in hepatic fractions from rats given 1,1,1,2-tetrafluoroethane (HFC-134a), which is not metabolized to a trifluoroacetyl halide. Because halothane hepatitis may be associated with an immune response directed against TFA-proteins in the livers of susceptible individuals, the quantity of TFA-proteins resulting from exposure to HCFCs or HFCs may be an important index for determining safe exposure limits for HCFCs or HFCs. C1 UNIV ROCHESTER,SCH MED,DEPT PHARMACOL,601 ELMWOOD AVE,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED,ENVIRONM HLTH SCI CTR,ROCHESTER,NY 14642. NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. GM CORP,RES LABS,DEPT BIOMED SCI,WARREN,MI 48090. FU NIEHS NIH HHS [ES07026, ES05407] NR 29 TC 57 Z9 59 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP-OCT PY 1992 VL 5 IS 5 BP 720 EP 725 DI 10.1021/tx00029a020 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA JN551 UT WOS:A1992JN55100020 PM 1446014 ER PT J AU FANANAPAZIR, L CHANG, AC EPSTEIN, SE MCAREAVEY, D AF FANANAPAZIR, L CHANG, AC EPSTEIN, SE MCAREAVEY, D TI PROGNOSTIC DETERMINANTS IN HYPERTROPHIC CARDIOMYOPATHY - PROSPECTIVE EVALUATION OF A THERAPEUTIC STRATEGY BASED ON CLINICAL, HOLTER, HEMODYNAMIC, AND ELECTROPHYSIOLOGICAL FINDINGS SO CIRCULATION LA English DT Article DE CARDIOMYOPATHIES; TACHYCARDIA, VENTRICULAR; DEATH, SUDDEN; PROGNOSIS ID SURVIVING CARDIAC-ARREST; SUDDEN-DEATH; ATRIAL-FIBRILLATION; ARRHYTHMIA; MANAGEMENT; SYNCOPE; PREVALENCE; STENOSIS; EXERCISE AB Background. Patients with hypertrophic cardiomyopathy (HCM) frequently have arrhythmias and hemodynamic abnormalities and are prone to sudden death and syncope. An important need exists for improved risk stratification and definition of appropriate investigation and therapy. Methods and Results. The relation of 31 clinical, Holter, cardiac catheterization, and electrophysiological (EP) variables to subsequent cardiac events in 230 HCM patients was examined by multivariate analysis. Studies were for cardiac arrest (n=32), syncope (n=80), presyncope (n=52), ventricular tachycardia (VT) on Holter (n=36), a strong family history of sudden death (n=9), and palpitations (n=21). Nonsustained VT on Holter was present in 115 patients (50%). Sustained ventricular arrhythmia was induced in 82 patients (36%). Seventeen cardiac events (eight sudden deaths, one cardiac arrest, and eight syncope with defibrillator discharges) occurred during a follow-up of 28+/-19 months. The 1-year and 5-year event-free rates were 99% and 79%, respectively. Two variables were significant independent predictors of subsequent events: sustained ventricular arrhythmia induced at EP study (beta, 3.5; p=0.002) and a history of cardiac arrest or syncope (beta, 2.9; p < 0.05). Only two of 66 patients without symptoms of impaired consciousness had a cardiac event (3-year event-free mte, 97%). In contrast, nonsustained VT on Holter was associated with a worse prognosis only in patients with symptoms of impaired consciousness: 11 of 79 symptomatic patients with VT on Holter (14%) had events versus only four of 85 symptomatic patients without VT on Holter (5%) (p=0.057). Notably, none of 51 patients without symptoms of impaired consciousness in whom VT was not induced at EP study had a cardiac event. Conclusions. In HCM, VT on Holter is of benign prognostic significance in the absence of symptoms of impaired consciousness and inducible VT, and sustained VT induced st EP study, especially when associated with cardiac arrest or syncope, identifies a subgroup at high risk for subsequent cardiac events. RP FANANAPAZIR, L (reprint author), NHLBI,CLIN ELECTROPHYSIOL LAB,CARDIOL BRANCH,ELECTROPHYSIOL SECT,ROOM 7B-14,BLDG 10,BETHESDA,MD 20892, USA. NR 37 TC 168 Z9 178 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP PY 1992 VL 86 IS 3 BP 730 EP 740 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JM270 UT WOS:A1992JM27000003 PM 1516184 ER PT J AU ETTINGER, WH WAHL, PW KULLER, LH BUSH, TL TRACY, RP MANOLIO, TA BORHANI, NO WONG, ND OLEARY, DH FURBERG, CD BOND, ME HEISS, G KLOPFENSTEIN, S LYLES, M MITTELMARK, M TELL, GS TOOLE, JF CODY, M GARNER, G CRUISE, G ROBBINS, J BOMMER, W LEE, M SCHENKER, MB TUPPER, CJ HIMMELMANN, T LABAW, F KAY, J BORHANI, P FRIED, LP COMSTOCK, GW GERMAN, PS KITTNER, SJ KUMANYIKA, S PRICE, TR ROCK, RC BRYAN, RN SZKLO, M TABATZNIK, B TOCKMAN, MS HILL, J CHABOT, JB CAULEY, J MATTHEWS, K NEWMAN, A ORCHARD, TJ RUTAN, GH SCHULZ, R SMITH, VE WOLFSON, SK MEYER, P MCLAUGHLIN, B GARDIN, JM ANTONCULVER, H HENRY, WL LOBODZINSKI, S WHITTENBERGER, J KNOLL, P CONNER, J POLAK, JF POTTER, J BOVILL, E CORNELL, E ENRIGHT, P TOOGOOD, S RAUTAHARJU, P RAUTAHARJU, F KRONMAL, RA PSATY, BM SISCOVICK, D HERMANSON, B SAVAGE, PJ SMITH, P AF ETTINGER, WH WAHL, PW KULLER, LH BUSH, TL TRACY, RP MANOLIO, TA BORHANI, NO WONG, ND OLEARY, DH FURBERG, CD BOND, ME HEISS, G KLOPFENSTEIN, S LYLES, M MITTELMARK, M TELL, GS TOOLE, JF CODY, M GARNER, G CRUISE, G ROBBINS, J BOMMER, W LEE, M SCHENKER, MB TUPPER, CJ HIMMELMANN, T LABAW, F KAY, J BORHANI, P FRIED, LP COMSTOCK, GW GERMAN, PS KITTNER, SJ KUMANYIKA, S PRICE, TR ROCK, RC BRYAN, RN SZKLO, M TABATZNIK, B TOCKMAN, MS HILL, J CHABOT, JB CAULEY, J MATTHEWS, K NEWMAN, A ORCHARD, TJ RUTAN, GH SCHULZ, R SMITH, VE WOLFSON, SK MEYER, P MCLAUGHLIN, B GARDIN, JM ANTONCULVER, H HENRY, WL LOBODZINSKI, S WHITTENBERGER, J KNOLL, P CONNER, J POLAK, JF POTTER, J BOVILL, E CORNELL, E ENRIGHT, P TOOGOOD, S RAUTAHARJU, P RAUTAHARJU, F KRONMAL, RA PSATY, BM SISCOVICK, D HERMANSON, B SAVAGE, PJ SMITH, P TI LIPOPROTEIN LIPIDS IN OLDER-PEOPLE - RESULTS FROM THE CARDIOVASCULAR HEALTH STUDY SO CIRCULATION LA English DT Article DE CHOLESTEROL; AGING; RISK FACTORS ID CORONARY HEART-DISEASE; HIGH BLOOD CHOLESTEROL; BODY-FAT DISTRIBUTION; RISK-FACTORS; SERUM-CHOLESTEROL; PLASMA-LIPIDS; ELDERLY MEN; WOMEN; TRIGLYCERIDES; DEATH AB Background. Cardiovascular disease is the leading cause of death and disability in older people. There is little information about the distributions of risk factors in older populations. This article describes the distribution and correlates of lipoprotein lipids in people greater-than-or-equal-to 65 years old. Methods and Results. Lipoprotein lipid concentrations were measured in 2,106 men (M) and 2,732 women (F) who were participants in the Cardiovascular Health Study, a population-based epidemiological study. Distributions of lipids by age and sex and bivariate and multivariate relations among lipids and other variables were determined in cross-sectional analyses. Mean concentrations of lipids were cholesterol: M, 5.20+/-0.93 mmol/l (201+/-36 mg/dl) and F, 5.81+/-0.98 mmol/l (225+/-38 mg/dl); triglyceride (TG): M, 1.58+/-0.85 mmol/l (140+/-75 mg/dl) and F, 1.57+/-0.78 mmol/l (139+/-69 mg/dl); high density lipoprotein cholesterol (HDL-C): M, 1.23+/-0.33 mmol/l (48+/-16 mg/dl), and F, 1.53+/-0.41 mmol/l (59+/-16 mg/dl); low density lipoprotein cholesterol (LDL-C): M, 3.27+/-0.85 mmol/l (127+/-33 mg/dl) and F, 3.57+/-0.93 mmol/l (138+/-36 mg/dl). The total cholesterol to HDL-C ratios were M, 4.49+/-1.29 and F, 4.05+/-1.22. TG, total cholesterol, and LDL-C concentrations were lower with increasing age, the last more evident in men than in women. TG concentration was positively associated with obesity (in women), central fat patterning, glucose intolerance, use of beta-blockers (in men), and use of estrogens (in women) and negatively associated with age, renal function, alcohol use, and socioeconomic status. In general, HDL-C had opposite relations with these variables, except that estrogen use was associated with higher HDL-C concentrations. LDL-C concentration was associated with far fewer variables than the other lipids but was negatively associated with age in men and women and positively correlated with obesity and central fat patterning and negatively correlated with renal function and estrogen use in women. There were no differences in total cholesterol and LDL-C concentrations among participants with and without prevalent coronary heart disease and stroke, but TG concentration was higher and HDL-C lower in men with both coronary heart disease and stroke and in women with coronary heart disease. Conclusions. Cholesterol and cholesterol/HDL-C ratio were lower and HDL-C higher than previously reported values in older people, suggesting that lipid risk profiles may be improving in older Americans. TG and HDL-C concentrations, and to a lesser extent LDL-C, were associated with potentially important modifiable factors such as obesity, glucose intolerance, renal function, and medication use. C1 UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98105. WAKE FOREST UNIV,DEPT INTERNAL MED,WINSTON SALEM,NC 27109. WAKE FOREST UNIV,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27109. UNIV PITTSBURGH,DEPT EPIDEMIOL,PITTSBURGH,PA 15260. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. UNIV VERMONT,DEPT PATHOL,BURLINGTON,VT 05405. UNIV VERMONT,DEPT BIOCHEM,BURLINGTON,VT 05405. NHLBI,DEPT EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV CALIF IRVINE,DEPT MED,IRVINE,CA 92717. HARVARD UNIV,DEPT RADIOL,CAMBRIDGE,MA 02138. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. UNIV CALIF DAVIS,DAVIS,CA 95616. NEW ENGLAND DEACONESS HOSP,CTR ULTRA SOUND READING,BOSTON,MA 02215. UNIV CALIF IRVINE,CTR ECHOCARDIOG READING,IRVINE,CA 92717. UNIV VERMONT,CENT BLOOD ANAL LAB,BURLINGTON,VT 05405. MAYO CLIN & MAYO FDN,CTR PULM FUNCT READING,ROCHESTER,MN 55905. UNIV ALBERTA,CTR ELECTRO CARDIOG READING,EDMONTON T6G 2E1,ALBERTA,CANADA. NHLBI,PROJECT OFF,BETHESDA,MD 20892. RP ETTINGER, WH (reprint author), UNIV WASHINGTON,CHS COORDINATING CTR,JD-36,1107 NE 45TH ST,SUITE 530,SEATTLE,WA 98105, USA. RI Tell, Grethe/G-5639-2015; Cauley, Jane/N-4836-2015 OI Tell, Grethe/0000-0003-1386-1638; Cauley, Jane/0000-0003-0752-4408 FU NHLBI NIH HHS [N01-HC-87079, N01-HC-87080, N01-HC-87081] NR 61 TC 114 Z9 120 U1 0 U2 5 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP PY 1992 VL 86 IS 3 BP 858 EP 869 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JM270 UT WOS:A1992JM27000018 PM 1516198 ER PT J AU DILSIZIAN, V FREEDMAN, NMT BACHARACH, SL PERRONEFILARDI, P BONOW, RO AF DILSIZIAN, V FREEDMAN, NMT BACHARACH, SL PERRONEFILARDI, P BONOW, RO TI REGIONAL THALLIUM UPTAKE IN IRREVERSIBLE DEFECTS - REPLY SO CIRCULATION LA English DT Letter ID VIABLE MYOCARDIUM; REINJECTION RP DILSIZIAN, V (reprint author), NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP PY 1992 VL 86 IS 3 BP 1043 EP 1044 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JM270 UT WOS:A1992JM27000043 ER PT J AU HAIGNEY, MCP MIYATA, H LAKATTA, EG STERN, MD SILVERMAN, HS AF HAIGNEY, MCP MIYATA, H LAKATTA, EG STERN, MD SILVERMAN, HS TI DEPENDENCE OF HYPOXIC CELLULAR CALCIUM LOADING ON NA+-CA-2+ EXCHANGE SO CIRCULATION RESEARCH LA English DT Article DE NA+-CA-2+ EXCHANGE; HYPOXIA; ISCHEMIA ID RAT HEART-CELLS; ISOLATED RABBIT HEART; INTRACELLULAR SODIUM; VENTRICULAR MYOCYTES; CONTRACTILE FAILURE; CARDIAC MYOCYTES; OXYGEN PARADOX; REOXYGENATION; AMILORIDE; MECHANISM AB Na+-Ca2+ exchange has been shown to contribute to reperfusion- and reoxygenation-induced cellular Ca2+ loading and damage in the heart. Despite the fact that both [Na+]i and [Ca2+]i have been documented to rise during ischemia and hypoxia, it remains unclear whether the rise in [Ca2+]i occurring during hypoxia is linked to the rise in [Na+]i via Na+-Ca2+ exchange before reoxygenation and how this relates to cellular injury. Single electrically stimulated (0.2 Hz) adult rat cardiac myocytes loaded with Na+-sensitive benzofuran isophthalate (SBFI), the new fluorescent probe, were exposed to glucose-free hypoxia (Po2<0.02 mm Hg), and SBFI fluorescence was monitored to index changes in [Na+]i. Parallel experiments were performed with indo-1-loaded cells to index [Ca2+]i. The SBFI fluorescence ratio (excitation, 350/380 nm) rose significantly during hypoxia after the onset of ATP-depletion contracture, consistent with a rise in [Na+]i. At reoxygenation, the ratio fell rapidly toward baseline levels. The indo-1 fluorescence ratio (emission, 410/490 nm) also rose only after the onset of rigor contracture and then often showed a secondary rise early after reoxygenation at a time when [Na+]i fell. The increase in both [Na+]i and [Ca2+]i, seen during hypoxia, could be markedly reduced by performing experiments in Na+-free buffer. These experiments suggested that hypoxic Ca2+ loading is linked to a rise in Na+i via Na+-Ca2+ exchange. To show that Na+-Ca2+ exchange activity was not fully inhibited by profound intracellular ATP depletion, cells were exposed to cyanide, and then buffer Na+ was abruptly removed after contracture occurred. The sudden removal of buffer Na+ would be expected to stimulate cell Ca2+ entry via Na+-Ca2+ exchange. A large rapid rise in the indo-1 fluorescence ratio ensued, which was consistent with abrupt cell Ca2+ loading via the exchanger. The effect of reducing hypoxic buffer [Na+] on cell morphology after reoxygenation was examined. Ninety-five percent of cells studied in a normal Na+-containing buffer (144 mM NaCl, n = 38) and reoxygenated 30 minutes after the onset of hypoxic rigor underwent hypercontracture. Only 12% of cells studied in Na+-free buffer (144 mM choline chloride, n = 17) hypercontracted at reoxygenation (p<0.05). Myocytes were also exposed to hypoxia in the presence of R 56865, a compound that blocks noninactivating components of the Na+ current. R 56865 blunted the rise in [Na+]i typically seen after the onset of rigor, suggesting that Na+ entry may occur, in part, through voltage-gated Na+ channels. These experiments provide evidence that [Na+]i rises during hypoxia and leads to cellular Ca2+ loading and cell destruction via Na+-Ca2+ exchange. Prevention of the rise in [Na+]i during hypoxia reduces cellular injury in this model. Further studies are required to fully elucidate the mechanisms underlying the rise in [Na+]i that occurs during hypoxia and ischemia. C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DIV CARDIOL,BALTIMORE,MD 21205. FU NHLBI NIH HHS [KO8 HL-02539, P50 HL-17655, R01 HL-42050] NR 37 TC 139 Z9 145 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP PY 1992 VL 71 IS 3 BP 547 EP 557 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA JJ592 UT WOS:A1992JJ59200007 PM 1323432 ER PT J AU MIYATA, H LAKATTA, EG STERN, MD SILVERMAN, HS AF MIYATA, H LAKATTA, EG STERN, MD SILVERMAN, HS TI RELATION OF MITOCHONDRIAL AND CYTOSOLIC FREE CALCIUM TO CARDIAC MYOCYTE RECOVERY AFTER EXPOSURE TO ANOXIA SO CIRCULATION RESEARCH LA English DT Article DE MITOCHONDRIAL [CA-2+]; CYTOSOLIC [CA-2+]; INDO-1; ANOXIA; REOXYGENATION ID RAT-HEART-CELLS; VENTRICULAR MYOCYTES; INTRACELLULAR SODIUM; CONTRACTILE FAILURE; RUTHENIUM RED; INJURY; REOXYGENATION; MAGNESIUM; TRANSPORT; REPERFUSION AB Mitochondrial calcium overload has been suggested as a marker for irreversible injury in the ischemic heart. A new technique is used to measure dynamic changes in mitochondrial free calcium concentration ([Ca2+]m) in electrically stimulated (0.2 Hz) adult rat cardiac myocytes during exposure to anoxia and reoxygenation. Cells were incubated with indo-1 AM, which distributes in both the cytosol and mitochondria. After Mn2+ quenching of the cytosolic signal, cells were exposed to anoxia, and the residual fluorescence was monitored. [Ca2+]m averaged 94 +/- 3 nM (n=16) at baseline, less than the baseline diastolic cytosolic free calcium concentration ([Ca2+]c, 124 +/- 4 nM, n=12), which was measured in cells loaded with the pentapotassium salt of indo-1. [Ca2+]m and [Ca2+]c rose steadily only after the onset of ATP-depletion rigor contracture. At reoxygenation 35 minutes later, [Ca2+]c fell rapidly to preanoxic levels and then often showed a transient further rise. In contrast, [Ca2+]m showed only a slight transient fall and a secondary rise at reoxygenation. At reoxygenation, cells immediately either recovered, demonstrating partial relengthening and retaining their rectangular shape and response to stimulation, or they hypercontracted to rounded dysfunctional forms. Recovery occurred only in cells in which [Ca2+]m or [Ca2+]c remained below 250 nM before reoxygenation. Early during reoxygenation, [Ca2+]m remained higher in cells that hypercontracted (305 +/- 36 nM) than in cells that recovered (138 +/- 9 nM, p<0.05), whereas [Ca2+]c did not differ between the two groups (156 +/- 10 versus 128 +/- 10 nM, respectively;p=NS). The role of the sarcoplasmic reticulum in Ca2+ regulation was evaluated in cells (n=16) pretreated with thapsigargin, an inhibitor of the sarcoplasmic reticulum Ca2+-ATPase. During anoxia [Ca2+]c and [Ca2+]m rose as they did without thapsigargin pretreatment. At reoxygenation, the rapid fall in [Ca2+]c was blunted, and [Ca2+]m showed an immediate increase in these cells, demonstrating the importance of the sarcoplasmic reticulum in postanoxic Ca2+ regulation. In summary, cellular hypercontracture is not associated with a sudden and massive rise in [Ca2+]c immediately after reoxygenation. The basis for the relation between [Ca2+]m and cellular recovery as well as the mechanisms underlying the observed changes in [Ca2+]m remain to be defined. C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DIV CARDIOL,BALTIMORE,MD 21205. FU NHLBI NIH HHS [R01 HL-42050, KO8 HL-02539] NR 41 TC 172 Z9 177 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP PY 1992 VL 71 IS 3 BP 605 EP 613 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA JJ592 UT WOS:A1992JJ59200013 PM 1499108 ER PT J AU BIRO, S SIEGALL, CB FU, YM SPEIR, E PASTAN, I EPSTEIN, SE AF BIRO, S SIEGALL, CB FU, YM SPEIR, E PASTAN, I EPSTEIN, SE TI INVITRO EFFECTS OF A RECOMBINANT TOXIN TARGETED TO THE FIBROBLAST GROWTH-FACTOR RECEPTOR ON RAT VASCULAR SMOOTH-MUSCLE AND ENDOTHELIAL-CELLS SO CIRCULATION RESEARCH LA English DT Article DE PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY; RESTENOSIS; PSEUDOMONAS EXOTOXIN; ACIDIC FIBROBLAST GROWTH FACTOR; ANGIOPLASTY; VASCULAR SMOOTH MUSCLE CELLS ID LUMINAL CORONARY ANGIOPLASTY; ANGIOGRAPHIC FOLLOW-UP; PSEUDOMONAS EXOTOXIN; ARTERIAL INJURY; CELLULAR PROLIFERATION; CYTOTOXIC ACTIVITY; CHIMERIC TOXIN; TIME COURSE; FACTOR-I; RESTENOSIS AB The dominant mechanism responsible for restenosis after angioplasty is believed to be the activation of medial smooth muscle cells (SMCs), leading to their proliferation, migration to the subintima, and further proliferation. To develop novel strategies that might inhibit or prevent restenosis, we previously used a chimeric toxin composed of transforming growth factor-alpha (which targets the epidermal growth factor receptor) and mutated Pseudomonas exotoxin to preferentially recognize and kill rapidly proliferating, versus quiescent, vascular SMCs. We have recently cloned and expressed a recombinant gene encoding Pseudomonas exotoxin with a mutated (nonfunctional) cell recognition domain fused with the ligand acidic fibroblast growth factor, termed aFGF-PE66(4Glu)KDEL; thus, this recombinant toxin targets the fibroblast growth factor receptor. In the present study, we evaluated the relative effects of this chimeric toxin on quiescent versus rapidly proliferating vascular SMCs and also determined whether aFGF-PE66(4Glu)KDEL exerted different effects on SMCs versus endothelial cells. Rapidly proliferating SMCs (grown in 10% fetal bovine serum) were very sensitive to the cytotoxic effects of aFGF-PE66(4Glu)KDEL, whereas cytotoxicity was significantly less when the SMCs were in a quiescent state (grown in medium supplemented with 0.5% fetal bovine serum). The chimeric toxin was also significantly less cytotoxic against endothelial cells. Competition studies using excess acidic fibroblast growth factor indicated that the cytotoxic effects are specifically mediated by the fibroblast growth factor receptor. Thus, the present studies suggest a potentially expanded role of recombinant toxin therapy in restenosis: multiple receptors can be targeted, and cytotoxic effects, at least in vitro, can be preferentially directed to rapidly proliferating vascular SMCs, with relative sparing of vascular endothelial cells. It will next be necessary to test this strategy for inhibiting restenosis in an in vivo model of vascular injury and SMC proliferation. C1 BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,WALLINGFORD,CT. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG,BETHESDA,MD 20892. RP BIRO, S (reprint author), NCI,CARDIOL BRANCH,BETHESDA,MD 20892, USA. NR 52 TC 31 Z9 31 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP PY 1992 VL 71 IS 3 BP 640 EP 645 PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA JJ592 UT WOS:A1992JJ59200017 PM 1323436 ER PT J AU KUEHR, J KARMAUS, W FRISCHER, T HENDELKRAMER, A WEISS, K MOSELER, M STEPHAN, V FORSTER, J URBANEK, R AF KUEHR, J KARMAUS, W FRISCHER, T HENDELKRAMER, A WEISS, K MOSELER, M STEPHAN, V FORSTER, J URBANEK, R TI LONGITUDINAL VARIABILITY OF SKIN PRICK TEST-RESULTS SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article ID POPULATION-SAMPLE; TEST REACTIVITY; BRONCHIAL HYPERRESPONSIVENESS; AUSTRALIAN SCHOOLCHILDREN; SYMPTOMS; CHILDREN; ASTHMA; REPRODUCIBILITY; DISORDERS; ATOPY AB The skin prick test (SPT) is a commonly used procedure for assessing a specific sensitization. The longitudinal variability of test results is of interest for clinical as well as epidemiological investigations. The sensitization to four common aeroallergens (grass pollen, birch pollen, Dermatophagoides pteronyssinus, cat dander) is investigated within the framework of three consecutive SPTs at 11-month intervals for a population of 587 schoolchildren. The prevalence of sensitization based on a weal diameter of at least 2 mm was between 12.9% (cat dander) and 23.9% (grass pollen) in the initial testing. The positive predictive values of the initial SPT were between 75.3% (birch pollen) and 88.2% (cat dander) for the two subsequent SPTs. In the case of initially negative tests with positive second and third SPTs the incidence ranged between 3.2% (cat dander) and 4.3% (birch pollen) per year. A clear increase in the intensity of reaction in subsequent tests was observed in a number of probands testing positively in the initial SPT. In conclusion, our data indicate a high long-term stability of a specific sensitization to aeroallergens in SPT. C1 UNIV HAMBURG,CHILDRENS HOSP,NORDIG,INST HLTH RES,W-2000 HAMBURG 13,GERMANY. NIH,BETHESDA,MD 20892. UNIV VIENNA,CHILDRENS HOSP,A-1010 VIENNA,AUSTRIA. RP KUEHR, J (reprint author), UNIV FREIBURG,CHILDRENS HOSP,MATHILDENSTR 1,W-7800 FREIBURG,GERMANY. NR 19 TC 41 Z9 41 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD SEP PY 1992 VL 22 IS 9 BP 839 EP 844 DI 10.1111/j.1365-2222.1992.tb02829.x PG 6 WC Allergy; Immunology SC Allergy; Immunology GA JP428 UT WOS:A1992JP42800005 PM 1422941 ER PT J AU LOCKSHIN, MD AF LOCKSHIN, MD TI TREATMENT OF LUPUS PREGNANCY - CAN WE REACH CONSENSUS SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Editorial Material ID ERYTHEMATOSUS RP LOCKSHIN, MD (reprint author), NIAMSD,BETHESDA,MD 20892, USA. NR 9 TC 8 Z9 8 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD SEP-OCT PY 1992 VL 10 IS 5 BP 429 EP 431 PG 3 WC Rheumatology SC Rheumatology GA JT603 UT WOS:A1992JT60300001 PM 1458694 ER PT J AU MANOLIO, TA BURKE, GL SAVAGE, PJ JACOBS, DR SIDNEY, S WAGENKNECHT, LE ALLMAN, RM TRACY, RP AF MANOLIO, TA BURKE, GL SAVAGE, PJ JACOBS, DR SIDNEY, S WAGENKNECHT, LE ALLMAN, RM TRACY, RP TI SEX-RELATED AND RACE-RELATED DIFFERENCES IN LIVER-ASSOCIATED SERUM CHEMISTRY TESTS IN YOUNG-ADULTS IN THE CARDIA STUDY SO CLINICAL CHEMISTRY LA English DT Note DE SCREENING; REFERENCE INTERVAL; VARIATION, SOURCE OF; POPULATION STUDIES ID REFERENCE INTERVALS; BLOOD-CHEMISTRY; ALCOHOL INTAKE; AGE; POPULATION; PROFILES; HEALTH; VALUES; RANGES AB Simultaneous multiple automated analyses of liver function can be performed quickly and cheaply, but their usefulness in mass screening is questionable. Reference intervals are frequently applied without regard to race and sex, despite the fact that reported values may vary considerably in relation to these factors. Serum analyte results for >5000 black and white men and women in the CARDIA Study showed clinically and statistically significant differences by race and sex for values of aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, total bilirubin, total protein, and albumin; these differences were not explained by differences in age, body mass, reported ethanol intake, smoking, or oral contraceptive use. Results for at least one of these six tests were out of range in 38% of the men and 19% of the women. Sex- and race-specific reference intervals are recommended to decrease the frequency of values reported as abnormal in otherwise healthy young adults. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,EBP,CLIN & GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. KAISER PERMANENTE,DIV RES,OAKLAND,CA 94611. UNIV ALABAMA,DIV GERONTOL & GERIATR MED,BIRMINGHAM,AL 35294. VET AFFAIRS MED CTR,BIRMINGHAM,AL 35205. UNIV VERMONT,DEPT PATHOL,BURLINGTON,VT 05405. RI Allman, Richard/D-5964-2011 FU NHLBI NIH HHS [N01-HC-84048, N01-HC-84047, N01-HC-84049] NR 34 TC 48 Z9 49 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 1992 VL 38 IS 9 BP 1853 EP 1859 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA JN322 UT WOS:A1992JN32200046 PM 1526025 ER PT J AU YECHOURON, A LEFEBVRE, J ROBSON, HG ROSE, DL TULLY, JG AF YECHOURON, A LEFEBVRE, J ROBSON, HG ROSE, DL TULLY, JG TI FATAL SEPTICEMIA DUE TO MYCOPLASMA-ARGININI - A NEW HUMAN ZOONOSIS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HOMINIS SEPTICEMIA; RESPIRATORY-TRACT; INFLAMMATORY POLYARTHRITIS; GENITAL MYCOPLASMAS; HYPOGAMMAGLOBULINEMIA; UREAPLASMA; SUSCEPTIBILITY; PATHOGENICITY; ARTHRITIS; PNEUMONIAE AB A 64-year-old slaughterhouse worker with advanced non-Hodgkin's lymphoma developed septicemia and pneumonia. Mycoplasma arginini, a wall-free prokaryote found in a variety of domestic animal hosts, was repeatedly isolated from blood and bronchial washings from the patient. Immunosuppression, in part caused by hypogammaglobulinemia, probably played a key role in predisposing the patient to a fatal infection. This case suggests that animal mycoplasmas should be considered in the list of infectious agents acquired by immunosuppressed hosts. C1 ROYAL VICTORIA HOSP,DEPT MED,DIV INFECT DIS,MONTREAL H3A 1A1,QUEBEC,CANADA. ROYAL VICTORIA HOSP,DEPT MICROBIOL,MONTREAL H3A 1A1,QUEBEC,CANADA. LAB SANTE PUBL QUEBEC,CHLAMYDIA UREAPLASMA PROGRAM,ST ANNE BELLEVUE,QUEBEC,CANADA. NIAID,MYCOPLASMA SECT,FREDERICK,MD 21701. NR 62 TC 23 Z9 24 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1992 VL 15 IS 3 BP 434 EP 438 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JK474 UT WOS:A1992JK47400009 PM 1520790 ER PT J AU ROLIDES, E PIZZO, PA AF ROLIDES, E PIZZO, PA TI MODULATION OF HOST DEFENSES BY CYTOKINES - EVOLVING ADJUNCTS IN PREVENTION AND TREATMENT OF SERIOUS INFECTIONS IN IMMUNOCOMPROMISED HOSTS SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID COLONY-STIMULATING FACTOR; RECOMBINANT HUMAN GRANULOCYTE; TUMOR-NECROSIS-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; BONE-MARROW TRANSPLANTATION; CHRONIC GRANULOMATOUS-DISEASE; HUMAN MONONUCLEAR PHAGOCYTES; HUMAN INTERFERON-GAMMA; BLOOD POLYMORPHONUCLEAR NEUTROPHILS; IMMUNE-DEFICIENCY SYNDROME AB Traditional management of infectious complications, especially in immunocompromised hosts, has depended on the prompt initiation of therapy with broad-spectrum antibiotics. During the past several years, however, a number of cytokines (interleukins, hematopoietic growth factors, interferons) have been developed and produced by recombinant DNA technology, and preclinical and clinical studies of cytokines in immunocompromised hosts have begun. The data being generated suggest that certain cytokines can accelerate neutrophil and monocyte/macrophage production, enhance their function, and potentially decrease infectious complications. The role of these agents in both the prevention and treatment of infectious diseases represents an important research challenge and offers new approaches to the prevention and treatment of infection in immunocompromised hosts. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,RM 13N240,BETHESDA,MD 20892. NR 224 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1992 VL 15 IS 3 BP 508 EP 524 PG 17 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JK474 UT WOS:A1992JK47400021 ER PT J AU WILLIAMSON, PR AF WILLIAMSON, PR TI TREATMENT OF PAECILOMYCES-VARIOTI INFECTION - REPLY SO CLINICAL INFECTIOUS DISEASES LA English DT Letter RP WILLIAMSON, PR (reprint author), NIAID,CLIN INVEST LAB,BLDG 10,ROOM 11N107,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1992 VL 15 IS 3 BP 553 EP 553 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JK474 UT WOS:A1992JK47400030 ER PT J AU SEGAL, J AF SEGAL, J TI FREUD JEWISH IDENTITY - A CASE-STUDY IN THE IMPACT OF ETHNICITY - DILLER,JV SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP SEGAL, J (reprint author), NIMH,SCI & PUBL INFORMAT PROGRAMS,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD SEP PY 1992 VL 37 IS 9 BP 886 EP 886 PG 1 WC Psychology, Multidisciplinary SC Psychology GA JP549 UT WOS:A1992JP54900026 ER PT J AU SIRIO, CA TAJIMI, K TASE, C KNAUS, WA WAGNER, DP HIRASAWA, H SAKANISHI, N KATSUYA, H TAENAKA, N AF SIRIO, CA TAJIMI, K TASE, C KNAUS, WA WAGNER, DP HIRASAWA, H SAKANISHI, N KATSUYA, H TAENAKA, N TI AN INITIAL COMPARISON OF INTENSIVE-CARE IN JAPAN AND THE UNITED-STATES SO CRITICAL CARE MEDICINE LA English DT Article DE JAPAN; SEVERITY OF ILLNESS INDEX; PATIENT OUTCOME ASSESSMENT; EVALUATION STUDIES; PROGNOSIS; RISK; INTENSIVE CARE; CRITICAL CARE; HOSPITAL BED CAPACITY; CROSS-CULTURAL COMPARISON ID APACHE-II; SYSTEM; POPULATION; HOSPITALS AB Objective: The objective of this study was to compare the utilization of, and outcome from, critical care services in selected medical centers providing secondary and tertiary care in the United States and Japan. Design: Prospective data collection on 1,292 patients from each of the participating Japanese study hospitals in 1987 to 1989 and compared with the 5,030 patients in the United States 1982 Acute Physiology and Chronic Health Evaluation (APACHE II) database used to develop the APACHE II equation. Detailed organizational characteristics of the participating ICUs and hospitals were also obtained. Setting: Data collection took place in the ICUs of 13 U.S. hospitals and six Japanese hospitals. Patients. Data were collected on consecutive, unselected patients from medical, surgical, and mixed medical/surgical critical care units, with a spectrum of medical and surgical diagnoses. Measurements and Main Results: U.S. and Japanese ICUs have a similar array of diagnostic and therapeutic modalities. Only 2% (range 0.6 to 3.5) of beds in Japanese hospitals were designated to intensive care. The organization of the Japanese and U.S. ICUs varied by hospital. There were significantly fewer women admitted to Japanese ICUs and a substantially lower proportion of low-risk-of-death patients. Despite a rapidly aging population, there were relatively fewer elderly patients with chronic health ailments in the Japanese ICU population (8%) compared with the U.S. cohort (18%). Conclusions: In this sample of hospitals, similar high-technology critical care is available in the United States and Japan. Variations in utilization between the two countries represent differences in case mix and bed availability. The APACHE II equation stratified patients in the Japanese patient cohort across the full spectrum of increasing severity of illness. C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. TEIKYO UNIV,SCH MED,CTR CRIT CARE,TOKYO 173,JAPAN. FUKUSHIMA MED SCH,DEPT ANAESTHESIOL,FUKUSHIMA 960,JAPAN. CHIBA UNIV,DEPT EMERGENCY & CRIT CARE MED,CHIBA,JAPAN. TOKYO MED & DENT UNIV,INTENS CARE MED SECT,TOKYO 113,JAPAN. KUMAMOTO UNIV,DEPT EMERGENCY & CRIT CARE MED,KUMAMOTO 860,JAPAN. OSAKA UNIV HOSP,INTENS CARE UNIT,OSAKA,JAPAN. RP SIRIO, CA (reprint author), GEORGE WASHINGTON UNIV,ICU RES,2300 K ST NW,WASHINGTON,DC 20037, USA. NR 20 TC 71 Z9 76 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 1992 VL 20 IS 9 BP 1207 EP 1215 DI 10.1097/00003246-199209000-00006 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA JN869 UT WOS:A1992JN86900006 PM 1521435 ER PT J AU KAUFMAN, D LONGO, DL AF KAUFMAN, D LONGO, DL TI HODGKINS-DISEASE SO CRITICAL REVIEWS IN ONCOLOGY/HEMATOLOGY LA English DT Review ID BONE-MARROW TRANSPLANTATION; REED-STERNBERG CELLS; COMBINED MODALITY THERAPY; LYMPHOCYTE PREDOMINANCE TYPE; TERM FOLLOW-UP; ACUTE NONLYMPHOCYTIC LEUKEMIA; HIGH-DOSE CYCLOPHOSPHAMIDE; COLONY-STIMULATING FACTOR; IMMUNOGLOBULIN GENE REARRANGEMENTS; CROSS-RESISTANT CHEMOTHERAPY RP KAUFMAN, D (reprint author), NCI,DIV CANC TREATMENT,BLDG 31,RM 3A44,BETHESDA,MD 20892, USA. NR 321 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD SEP PY 1992 VL 13 IS 2 BP 135 EP 187 DI 10.1016/1040-8428(92)90021-H PG 53 WC Oncology; Hematology SC Oncology; Hematology GA JT736 UT WOS:A1992JT73600003 PM 1418644 ER PT J AU KASNER, L CHAN, CC CORDELLAMIELE, E GERY, I AF KASNER, L CHAN, CC CORDELLAMIELE, E GERY, I TI THE EFFECT OF CHLORPROMAZINE ON ENDOTOXIN-INDUCED UVEITIS IN THE LEWIS RAT SO CURRENT EYE RESEARCH LA English DT Article ID PHOSPHOLIPASE-A2; CELLS; SHOCK AB Chlorpromazine (CPZ) has been used extensively in the treatment of psychiatric disorders, and has recently been shown to possess systemic anti-inflammatory properties as well. To investigate the potential effects of CPZ on ocular inflammation, we evaluated its action on endotoxin-induced uveitis (EIU) in Lewis rats. At three different dosage levels, CPZ produced highly significant reductions in the mean aqueous aspirate inflammatory cell counts and histological inflammatory scores as compared to controls treated with vehicle only. Analysis of aqueous fluid demonstrated a similar decrease in protein concentration and phospholipase A2 (PLA-2) activity in the treated animals. The ability of CPZ to inhibit the development of EIU may be related to its properties as a calcium channel blocker and inhibitor of the enzyme phospholipase A2. C1 NEI,IMMUNOL LAB,BLDG 10,RM 10N202,BETHESDA,MD 20892. NICHHD,DEV GENET SECT,BETHESDA,MD 20892. NR 15 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD SEP PY 1992 VL 11 IS 9 BP 843 EP 848 DI 10.3109/02713689209033482 PG 6 WC Ophthalmology SC Ophthalmology GA JU196 UT WOS:A1992JU19600003 PM 1424727 ER PT J AU DUFF, GW OPPENHEIM, JJ AF DUFF, GW OPPENHEIM, JJ TI COMPARATIVE ASPECTS OF HOST-PARASITE AND HOST-TUMOR RELATIONSHIPS SO CYTOKINE LA English DT Editorial Material C1 NCI, FREDERICK, MD 21701 USA. RP DUFF, GW (reprint author), UNIV SHEFFIELD, ROYAL HALLAMSHIRE HOSP, SHEFFIELD S10 2JF, S YORKSHIRE, ENGLAND. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD SEP PY 1992 VL 4 IS 5 BP 331 EP 339 DI 10.1016/1043-4666(92)90075-3 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA JR616 UT WOS:A1992JR61600001 PM 1420993 ER PT J AU TOYODA, T WOLFFE, AP AF TOYODA, T WOLFFE, AP TI CHARACTERIZATION OF RNA POLYMERASE-II-DEPENDENT TRANSCRIPTION IN XENOPUS EXTRACTS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID MAJOR DEVELOPMENTAL TRANSITION; RIBONUCLEIC-ACID POLYMERASE; HEAT-SHOCK; GENE-EXPRESSION; DIFFERENTIAL EXPRESSION; MIDBLASTULA TRANSITION; INVITRO TRANSCRIPTION; LAEVIS EMBRYOGENESIS; REGULATORY SIGNALS; NUCLEAR EXTRACT C1 NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM 131,BETHESDA,MD 20892. NR 36 TC 26 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP PY 1992 VL 153 IS 1 BP 150 EP 157 DI 10.1016/0012-1606(92)90099-3 PG 8 WC Developmental Biology SC Developmental Biology GA JM416 UT WOS:A1992JM41600013 PM 1516744 ER PT J AU KELLY, D OREILLY, MA RIZZINO, A AF KELLY, D OREILLY, MA RIZZINO, A TI DIFFERENTIAL REGULATION OF THE TRANSFORMING GROWTH-FACTOR TYPE-BETA-2 GENE PROMOTER IN EMBRYONAL CARCINOMA-CELLS AND THEIR DIFFERENTIATED CELLS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID PARIETAL ENDODERM; FACTOR-BETA; STEM-CELLS; EXPRESSION; INDUCTION; FACTOR-BETA-3; ELEMENTS; CAMP C1 UNIV NEBRASKA,MED CTR,EPPLEY INST RES CANC & ALLIED DIS,600 S 42ND ST,OMAHA,NE 68198. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68198. FU NCI NIH HHS [CA 36727] NR 22 TC 23 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP PY 1992 VL 153 IS 1 BP 172 EP 175 DI 10.1016/0012-1606(92)90102-M PG 4 WC Developmental Biology SC Developmental Biology GA JM416 UT WOS:A1992JM41600016 PM 1516748 ER PT J AU LIU, QZ KNOWLER, WC NELSON, RG SAAD, MF CHARLES, MA LIEBOW, IM BENNETT, PH PETTITT, DJ AF LIU, QZ KNOWLER, WC NELSON, RG SAAD, MF CHARLES, MA LIEBOW, IM BENNETT, PH PETTITT, DJ TI INSULIN-TREATMENT, ENDOGENOUS INSULIN CONCENTRATION, AND ECG ABNORMALITIES IN DIABETIC PIMA-INDIANS - CROSS-SECTIONAL AND PROSPECTIVE ANALYSES SO DIABETES LA English DT Article ID CORONARY-HEART-DISEASE; CARDIOVASCULAR RISK-FACTORS; IMPAIRED GLUCOSE-TOLERANCE; MYOCARDIAL-INFARCTION; MACROVASCULAR DISEASE; FOLLOW-UP; HIGH PREVALENCE; MELLITUS; MORTALITY; HYPERTENSION AB The prevalence and incidence of CHD, defined by ECG abnormalities according to the Tecumseh criteria for Minnesota Codes, were determined in Pima Indians greater-than-or-equal-to 25 yr of age. In a cross-sectional analysis, the age-sex-adjusted prevalence (+/- SE) of ECG abnormalities was higher in 1454 NIDDM patients (6.86 +/- 0.65%) than in 1696 nondiabetic subjects (3.23 +/- 0.63%; prevalence rate ratio = 2.12; 95% CI 1.39-3.25). In a prospective analysis, the age-sex-adjusted incidence (+/- SE) of ECG abnormalities was higher in 824 NIDDM patients (12.77 +/- 1.67) than in 935 nondiabetic subjects (5.93 +/- 1.43 cases/1000 person-yr; incidence rate ratio = 2.15; 95% CI 1.26-3.69). The prevalence of ECG abnormalities in insulin-treated NIDDM patients was significantly higher than in NIDDM patients not treated with insulin (age-sex-adjusted OR = 2.83; 95% CI 1.84-4.33); and this association persisted when adjusted for other factors such as sBP, BMI, duration of diabetes, serum cholesterol concentration, and oral hypoglycemic agents (OR = 2.12; 95% CI 1.34-3.37). in the prospective analysis, the incidence of ECG abnormalities in NIDDM patients treated with insulin was higher than in those NIDDM patients not treated with insulin, but, when controlled for age, sex, duration of diabetes, and oral hypoglycemic agents in a proportional-hazards model, the relationship with insulin treatment was not statistically significant (incidence rate ratio = 1.36; 95% CI 0.80-2.31). This suggests that insulin treatment may be a marker of more severe diabetes, and that factors associated with clinical indications for insulin treatment, rather than insulin treatment per se, are related causally to CHD. On the other hand, endogenous fasting and 2-h postload serum insulin concentrations were not associated with ECG abnormalities among 761 NIDDM patients not treated with insulin nor among 1226 nondiabetic subjects. Furthermore, in the prospective study, neither endogenous fasting nor 2-h postload serum insulin was associated with the subsequent development of ECG abnormalities in NIDDM patients or nondiabetic subjects. C1 NIDDK,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DIABET & ARTHRIT EPIDEMIOL SECT,1550 E INDIAN SCH RD,PHOENIX,AZ 85014. CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,PHOENIX,AZ. RI Nelson, Robert/B-1470-2012 FU NIDDK NIH HHS [N01-DK-7-2291] NR 62 TC 62 Z9 62 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1992 VL 41 IS 9 BP 1141 EP 1150 DI 10.2337/diabetes.41.9.1141 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JK179 UT WOS:A1992JK17900017 PM 1499865 ER PT J AU KIKKAWA, R UMEMURA, K HANEDA, M KAJIWARA, N MAEDA, S NISHIMURA, C SHIGETA, Y AF KIKKAWA, R UMEMURA, K HANEDA, M KAJIWARA, N MAEDA, S NISHIMURA, C SHIGETA, Y TI IDENTIFICATION AND CHARACTERIZATION OF ALDOSE REDUCTASE IN CULTURED RAT MESANGIAL CELLS SO DIABETES LA English DT Article ID ALDEHYDE REDUCTASE; IMMUNOHISTOCHEMICAL LOCALIZATION; IMMUNOLOGICAL IDENTIFICATION; PERIPHERAL-NERVE; GLOMERULAR CELLS; ANGIOTENSIN-II; ORAL SORBINIL; COMPLICATIONS; PURIFICATION; PREVENTION AB Although the enhanced activity of the polyol pathway has been detected in diabetic glomeruli, the intraglomerular localization of this pathway has not yet been well defined. In this study, we attempted to identify aldose reductase, a key enzyme of the polyol pathway, in cultured rat mesangial cells and to characterize the properties of this enzyme using enzymological and immunological methods. When the aldose reductase (DL-glyceraldehyde-reducing) activity was analyzed in mesangial cell extract, the Lineweaver-Burk plot showed concave downward curvature, and the Michaelis constant was 0.83 mM DL-glyceraldehyde, and this activity was noncompetitively inhibited by an aldose reductase inhibitor, ICI-128,436. The enzyme activity was enhanced by the addition of sulfate ion and partially suppressed by barbital. The enzyme cross-reacted with the antisera against rat lens and testis aldose reductases on Ouchterlony plate, and migrated to the region of molecular weight of about 36,500 Da on Western blotting. The presence of aldose reductase mRNA was also confirmed by Northern analysis using cDNA for rat aldose reductase, 10Q. From these results, it was concluded that the aldose reductase may exist in rat glomerular mesangial cells and may play a role in the development of diabetic glomerulopathy, though the coexistence of aldehyde reductase(s) may not be fully ruled out. C1 NEI,BETHESDA,MD 20892. RP KIKKAWA, R (reprint author), SHIGA UNIV MED SCI,DEPT MED 3,OTSU,SHIGA 52021,JAPAN. NR 38 TC 24 Z9 24 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1992 VL 41 IS 9 BP 1165 EP 1171 DI 10.2337/diabetes.41.9.1165 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JK179 UT WOS:A1992JK17900020 PM 1499867 ER PT J AU GHANAYEM, BI SANCHEZ, IM BURKA, LT AF GHANAYEM, BI SANCHEZ, IM BURKA, LT TI EFFECTS OF DOSE, STRAIN, AND DOSING VEHICLE ON METHACRYLONITRILE DISPOSITION IN RATS AND IDENTIFICATION OF A NOVEL-EXHALED METABOLITE SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID TOXICITY AB Methacrylonitrile (MAN), an aliphatic nitrile used in the production of plastics and elastomers, is structurally related to the known animal carcinogen, acrylonitrile. Although MAN has potential to cause significant toxicity, minimal information is available on its toxicity or fate. Current studies were designed to investigate the biological fate of [2-C-14]MAN in male F344 rats. Following gavage administration of 115, 11.5, or 1.15 mg MAN/kg in water, male F344 rats were placed in glass metabolism cages and urine, expired air, and feces were collected. Rats were sacrificed at various times, and the concentration of MAN-derived radioactivity in tissues was determined. MAN was rapidly absorbed from the gastrointestinal tract and distributed to all major tissues. After gavage administration of 1.15-115 mg/kg, [2-C-14]MAN is primarily eliminated in the expired air. Sixty to 70% of the low and medium doses were exhaled as (CO2)-C-14 in 72 hr compared with 25% of the highest dose. Whereas 40% of the high dose was expired as organic volatiles in 72 hr, only 9-12% of the low and medium doses were exhaled as such. It is therefore apparent that saturation of MAN metabolism occurs at the high dose. HPLC analysis of expired organic volatiles from MAN-treated rats showed that it contained two components that were identified as unchanged MAN and acetone. The MAN:acetone ratio was directly proportional to dose and decreased as a function of time. Urinary excretion accounted for 20-30% of all MAN doses within 72 hr after dosing. Investigating the effect of dosing vehicle on MAN disposition in rats revealed that administration of 115 mg MAN/kg in oil resulted in the death of rats within 24 hr after treatment. Furthermore, monitoring the fate of MAN in these rats before death showed that a significantly higher percentage of the dose was eliminated in urine and expired air. Analysis of this expired air also revealed that significantly more acetone and less unchanged MAN were exhaled by these animals. It is apparent that administration of MAN to F344 rats in oil resulted in slower absorption, decreased elimination of unchanged MAN, and increased metabolism to acetone and/or decreased degradation of acetone to CO2. The combination of these effects of an oil vehicle may have contributed to the death of rats by MAN. Comparison of the metabolism and disposition of MAN in F344 and Sprague-Dawley rats showed minor differences between the two strains. Further, administration of MAN to Sprague-Dawley rats in oil caused minimal change in MAN disposition and had no lethal effect on this strain of rats compared with that caused in F344 rats. RP GHANAYEM, BI (reprint author), NIEHS,EXPTL TOXICOL BRANCH,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709, USA. NR 15 TC 17 Z9 17 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD SEP-OCT PY 1992 VL 20 IS 5 BP 643 EP 652 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JP162 UT WOS:A1992JP16200004 PM 1358567 ER PT J AU WHEELER, D TIETZ, D CHRAMBACH, A AF WHEELER, D TIETZ, D CHRAMBACH, A TI INFORMATION ON DNA CONFORMATION DERIVED FROM TRANSVERSE PORE GRADIENT GEL-ELECTROPHORESIS IN CONJUNCTION WITH AN ADVANCED DATA-ANALYSIS APPLIED TO CAPILLARY ELECTROPHORESIS IN POLYMER MEDIA SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT INTERNATIONAL MEETING : ELECTROPHORESIS FORUM 92 CY OCT 26-28, 1992 CL TECH UNIV MUNICH, MUNICH, GERMANY HO TECH UNIV MUNICH ID POLYACRYLAMIDE-GEL; FRAGMENTS; MICROSCOPY; SEPARATION; MOBILITY; ANGLES; FIELDS; MODEL AB Abnormally slow migration of DNA is conventionally viewed as being due to an abnormal conformation relative to "linear" standards. The evidence for this rests on a few instances where nonlinear DNA structures have been established by independent methods and yield low mobilities relative to standards. Transverse pore gradient gel electrophoresis of authentically bent kinetoplast DNA and of an upstream activator sequence (UAS) of an E. coli operon promoter shows in addition that curves of migration distance vs. gel concentration ("Ferguson curves") of such abnormally conformed DNA differ from those of "linear" standards. Since Ferguson curves are interpretable with regard to molecular size in concordance with a mathematical model (Ogston model), transverse pore gradient gel electrophoresis provides a simple means of correlating abnormally slow migration of DNA with molecular size. In addition, transverse pore gradient gel electrophoresis is able to distinguish between DNA banding which exhibits a steeper dependence on gel concentration than "linear" standards from one which shows the same dependence. The former appears characteristic of circularly bent DNA and gives rise to a substantial retardation, the latter of bending across a knot or kink in the DNA chain associated with a relatively minor retardation relative to standards. Circularly bent restriction fragments formed from kinetoplast DNA retain the characteristic intersecting Ferguson curves on the transverse pore gradient gel. Another authentically "abnormal" DNA structure recognizable on transverse pore gradient gels is supercoiled DNA derived from the reaction of topoisomerase with a plasmid. Different lengths of supercoiled sequences give rise to parallel Ferguson curves clearly intersecting with those of linear standards. Since the progressive stretching and/or orientation of DNA with increasing polymer concentration is suggested by the concave Ferguson plot of DNA and, derived from it, the plot of DNA radius vs. polymer concentration obtained for capillary zone electrophoresis data on uncrosslinked polyacrylamide and agarose solutions as well as the corresponding gels, the abnormal retardation of DNA relative to "linear" standards is being interpreted in terms of a lowered stretchability and/or orientability of abnormally conformed species as compared to "linear" ones. C1 NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,RM 6C101,BETHESDA,MD 20892. NR 28 TC 15 Z9 15 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD SEP-OCT PY 1992 VL 13 IS 9-10 BP 604 EP 608 DI 10.1002/elps.11501301122 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA JZ085 UT WOS:A1992JZ08500005 PM 1459073 ER PT J AU PULYAEVA, H WHEELER, D GARNER, MM CHRAMBACH, A AF PULYAEVA, H WHEELER, D GARNER, MM CHRAMBACH, A TI MOLECULAR-SIEVING OF LAMBDA PHAGE DNA IN POLYACRYLAMIDE SOLUTIONS AS A FUNCTION OF THE MOLECULAR-WEIGHT OF THE POLYMER SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT INTERNATIONAL MEETING : ELECTROPHORESIS FORUM 92 CY OCT 26-28, 1992 CL TECH UNIV MUNICH, MUNICH, GERMANY HO TECH UNIV MUNICH ID GEL-ELECTROPHORESIS; CAPILLARY ELECTROPHORESIS; RESTRICTION FRAGMENTS; SEPARATION; PARTICLES; SIZE; VISCOSITY; AGAROSE AB Electrophoresis of lambda phage DNA was carried out in solutions at various concentrations of uncrosslinked polyacrylamide of 0.6, 1, 5 and 9 X 10(6) molecular weight (M(w)) with narrow M(w) distribution. By inspection of mobilities in the various concentration ranges, it appears that mobilities decrease, and retardation increases, with increasing M(w). The relation between electrophoretic retardation and the M(w) of the polymer was also interpreted (i) in the manner previously applied to nonlinear Ferguson plots and compatible with the Ogston model; and (ii) empirically, on the basis of the first derivatives of the functions describing the Ferguson plots at the polymer concentrations used. Interpretation (i) shows that the retardation increases linearly in the order of 0.6, 1, 5 and 9 X 10(6) M(w) of polyacrylamide. Interpretation (ii) shows a nonlinear increase of retardation in the M(w) range 5 to 9 X 10(6), and a decrease in retardation as M(w) is raised from 0.6 to 5.0 X 10(6). Hypothetically, interpretation (ii) can be explained mechanistically by a progressive change, as the polymer size is increased, from a collision with the surface of the polymer fiber to one occurring after permeation in the interior of a random-coiled fiber. Interpretation (i) may fail to detect that change due to the large difference between DNA mobility in solutions of the smallest polymer and the free mobility. DNA peak detection in all of the four size classes of polyacrylamide in solution is limited to relatively narrow ranges of polymer concentration. For the electrophoresis of lambda DNA, polyacrylamide of 5 X 10(-6) M(w) represents an optimum due to a compromise between small mobility differences at various concentrations of the polymer with M(w) 0.6 X 10(6), either little retardation (interpretation (i)) or insufficient responsiveness of the Ferguson plot to concentration changes (interpretation (ii)) in presence of the polymer of 1 X 10(6) M(w) and an excessively narrow available concentration range at 9 x 10(6) M(w). A highly disperse solution of polyacrylamide of 18 X 10(6) molecular weight retarded lambda DNA only slightly. Retardation decreased upon ultrafiltration of the polymer solutions, presumably through the decrease of their concentrations or adsorption of the largest chains within the size distribution. C1 NICHHD,MACROMOLEC ANAL SECT,THEORET & PHYS BIOL LAB,BLDG 10,RM 6C-101,BETHESDA,MD 20892. NR 31 TC 25 Z9 25 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD SEP-OCT PY 1992 VL 13 IS 9-10 BP 608 EP 614 DI 10.1002/elps.11501301123 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA JZ085 UT WOS:A1992JZ08500006 PM 1459074 ER PT J AU TIETZ, D ALDROUBI, A PULYAEVA, H GUSZCZYNSKI, T GARNER, MM CHRAMBACH, A AF TIETZ, D ALDROUBI, A PULYAEVA, H GUSZCZYNSKI, T GARNER, MM CHRAMBACH, A TI ADVANCES IN DNA ELECTROPHORESIS IN POLYMER-SOLUTIONS SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT INTERNATIONAL MEETING : ELECTROPHORESIS FORUM 92 CY OCT 26-28, 1992 CL TECH UNIV MUNICH, MUNICH, GERMANY HO TECH UNIV MUNICH ID INFORMATION AB DNA electrophoresis in gels and solutions of agarose and polyacrylamide was objectively evaluated with regard to separation efficiency at optimal polymer concentrations. In application to DNA fragments, polyacrylamide gels were superior for separating fragments of less than 7800 bp, and agarose gels are the best choice for larger fragments. Agarose solutions are nearly as good as polyacrylamide gels for small DNA (< 300 bp). Agarose solutions have a higher efficiency than polyacrylamide solutions for DNA of less than 1200 bp. Separation efficiency sharply decreases with increasing length of DNA. Retardation in polyacrylamide solutions was found to depend on polymer length in a biphasic fashion. The choice of resolving polymer concentrations depends on the progressive stretching of DNA in proportion to polymer concentration. The rate of that stretching appears higher in polyacrylamide solution than in gels or in liquid or gelled agarose. Application of polymer solutions to capillary electrophoresis raises further problems concerning agarose plugs, DNA interactions with the polymers, operation at low field strength and long durations as well as detection sensitivity. C1 NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,RM 6C101,BETHESDA,MD 20892. RI Aldroubi, Akram/J-7186-2012 NR 11 TC 25 Z9 25 U1 0 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD SEP-OCT PY 1992 VL 13 IS 9-10 BP 614 EP 616 DI 10.1002/elps.11501301124 PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA JZ085 UT WOS:A1992JZ08500007 PM 1459075 ER PT J AU RUTLEDGE, T COSSON, P MANOLIOS, N BONIFACINO, JS KLAUSNER, RD AF RUTLEDGE, T COSSON, P MANOLIOS, N BONIFACINO, JS KLAUSNER, RD TI TRANSMEMBRANE HELICAL INTERACTIONS - ZETA-CHAIN DIMERIZATION AND FUNCTIONAL ASSOCIATION WITH THE T-CELL ANTIGEN RECEPTOR SO EMBO JOURNAL LA English DT Article DE DISULFIDE-LINKED DIMERS; T-CELL ANTIGEN RECEPTOR; TRANSMEMBRANE DOMAIN ID AFFINITY IGE RECEPTOR; NATURAL-KILLER CELLS; MOLECULAR-CLONING; FC-RECEPTOR; ETA-CHAIN; ENDOPLASMIC-RETICULUM; TCR/CD3 COMPLEX; GAMMA-SUBUNIT; CD3 COMPLEX; EXPRESSION AB Members of the zeta-family of receptor subunits (zeta, eta and gamma) are structurally related proteins found as components of the T cell antigen receptor (TCR) and certain Fc receptors. These proteins share the ability to form disulfide-linked dimers with themselves and with other members of the family. Comparison of the amino acid sequences of zeta and gamma reveals a significant degree of homology, which is highest within their membrane-spanning domains. Analysis of their transmembrane sequences on a helical wheel projection suggests that all of the identical amino acids are clustered on one face of a potential alpha-helix. This face contains the only cysteine residue within zeta, suggesting that this conserved region may function to mediate dimerization. Indeed, replacing the transmembrane domain of the Tac antigen (alpha-chain of the interleukin-2 receptor) by that of the zeta-chain resulted in the formation of disulfide-linked dimers of Tac. The conserved aspartic acid residue found in the zeta and gamma-transmembrane sequences was found to play a role in disulfide linkage. Replacing the aspartic acid with a lysine but not with an alanine or valine residue allowed formation of disulfide-linked dimers. The ability of the aspartic acid residue to support dimerization was dependent upon its position within the helix. Thus, these observations indicate that residues within the zeta-transmembrane domain play a critical role in the formation of disulfide-linked dimers. Expression of zeta-mutants in zeta-deficient T cells revealed that the zeta-transmembrane domain is also responsible for reconstituting transport of functional TCR complexes to the cell surface and differentiated the requirements for disulfide-linked dimerization per se from assembly of the TCR complex. RP RUTLEDGE, T (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 46 TC 91 Z9 91 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD SEP PY 1992 VL 11 IS 9 BP 3245 EP 3254 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JJ039 UT WOS:A1992JJ03900011 PM 1505516 ER PT J AU TAYLOR, JP POMERANTZ, R BAGASRA, O CHOWDHURY, M RAPPAPORT, J KHALILI, K AMINI, S AF TAYLOR, JP POMERANTZ, R BAGASRA, O CHOWDHURY, M RAPPAPORT, J KHALILI, K AMINI, S TI TAR-INDEPENDENT TRANSACTIVATION BY TAT IN CELLS DERIVED FROM THE CNS - A NOVEL MECHANISM OF HIV-1 GENE-REGULATION SO EMBO JOURNAL LA English DT Article DE HIV-1; TAR ELEMENT; TAT PROTEIN ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERMINAL REPEAT; TRANS-ACTIVATOR GENE; IMMUNE-DEFICIENCY SYNDROME; AIDS DEMENTIA COMPLEX; HUMAN GLIAL-CELLS; HTLV-III; PROGRESSIVE ENCEPHALOPATHY; PRODUCTIVE INFECTION; TRANSCRIPTION FACTOR AB The Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for productive infection and is a potential target for antiviral therapy. Tat, a potent activator of HIV-1 gene expression, serves to greatly increase the rate of transcription directed by the viral promoter. This induction, which seems to be an important component in the progression of acquired immune deficiency syndrome (AIDS), may be due to increased transcriptional initiation, increased transcriptional elongation, or a combination of these processes. Much attention has been focused on the interaction of Tat with a specific RNA target termed TAR (transactivation responsive) which is present in the leader sequence of atl HIV-1 mRNAs. This interaction is believed to be an important component of the mechanism of transactivation. In this report we demonstrate that in certain CNS-derived cells Tat is capable of activating HIV-1 through a TAR-independent pathway. A Tat-responsive element is found upstream within the viral promoter that in glial-derived cell lines allows transactivation in the absence of TAR. Deletion mapping and hybrid promoter constructs demonstrate that the newly identified Tat-responsive element corresponds to a sequence within the viral long terminal repeat (LTR) previously identified as the HIV-1 enhancer, or NF-chi-B domain. DNA band-shift analysis reveals NF-chi-B binding activity in glial cells that differs from that present in T lymphoid cells. Further, we observe that TAR-deleted mutants of HIV-1 demonstrate normal late gene expression in glial cells as evidenced by syncytia formation and production of viral p24 antigen. These results suggest that the upstream Tat-responsive element is sufficiently active to support viral replication and indicate that an alternative regulatory circuit influencing HIV-1 gene expression is operational within some cells. C1 THOMAS JEFFERSON UNIV,JEFFERSON INST MOLEC MED,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,DEPT MED,DIV INFECT DIS,PHILADELPHIA,PA 19107. NIDR,ORAL MED LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT MED,DIV RENAL DIS & HYPERTENS,WASHINGTON,DC 20037. FU NCI NIH HHS [CA47996]; NIAID NIH HHS [AI00930, AI28272] NR 69 TC 106 Z9 106 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD SEP PY 1992 VL 11 IS 9 BP 3395 EP 3403 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JJ039 UT WOS:A1992JJ03900027 PM 1505523 ER PT J AU ZERBINI, C KOZAKEWICH, HPW WEINBERG, DS MUNDT, DJ EDWARDS, JA LACK, EE AF ZERBINI, C KOZAKEWICH, HPW WEINBERG, DS MUNDT, DJ EDWARDS, JA LACK, EE TI ADRENOCORTICAL NEOPLASMS IN CHILDHOOD AND ADOLESCENCE - ANALYSIS OF PROGNOSTIC FACTORS INCLUDING DNA CONTENT SO ENDOCRINE PATHOLOGY LA English DT Article ID FLOW CYTOMETRIC ANALYSIS; ADRENAL-CORTICAL TUMORS; DEOXYRIBONUCLEIC-ACID PLOIDY; IMAGE-ANALYSIS; CELLULAR DNA; CARCINOMA; CHILDREN; CLASSIFICATION; PROLIFERATION; ANEUPLOIDY AB Thirty-two adrenocortical neoplasms in children and adolescents were evaluated for prognostic factors including clinical and morphological parameters and DNA ploidy. The patients were segregated into two groups according to clinical outcome: group A, represented by patients with clinically benign neoplasms (n = 15), and group B, patients with clinically malignant tumors as evidenced by local recurrence, metastases, or fatal outcome In = 17). Clinical and morphological parameters in these two groups were evaluated using appropriate statistical methods. Parameters with a significant predictive value in terms of prognosis were age (p = .04), tumor size (p = .0003), median tumor weight (p = .0001), mitotic count (p = 0.04), and 25% tumor necrosis or more (p = .03). Twenty-three cases were studied for DNA ploidy: 10 cases by image analysis and 13 by both image analysis and flow cytometry. By ploidy analysis, 17 of 23 cases-12 of 14 in group A and 5 of 9 in group B-were found to be aneuploid. Multiple aneuploid peaks were found in 5 of 23 cases-4 of 14 cases in group A and 1 of 9 cases in group B. In tumors studied by both image analysis and flow cytometry, there was no discrepancy between results of ploidy analysis. There was no statistically significant association demonstrated between clinical outcome and DNA ploidy pattern. DNA ploidy heterogeneity, characterized by multiple aneuploid populations of cells, was also detected in both benign and malignant neoplasms. Based on our results, aneuploidy is relatively frequent in pediatric adrenocortical tumors and does not appear to have predictive value for biological behavior. C1 GEORGETOWN UNIV, SCH MED,DEPT PATHOL,BASIC SCI BLDG RM 161, 3900 RESERVOIR RD NW, WASHINGTON, DC 20007 USA. HARVARD UNIV, CHILDRENS HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. GEORGETOWN UNIV, SCH MED, DEPT BIOSTAT, WASHINGTON, DC 20007 USA. NCI, BETHESDA, MD 20892 USA. RI Zerbini, Maria Claudia/D-1586-2012 OI Zerbini, Maria Claudia/0000-0002-7408-9816 NR 32 TC 10 Z9 10 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 EI 1559-0097 J9 ENDOCR PATHOL JI Endocr. Pathol. PD SEP PY 1992 VL 3 IS 3 BP 116 EP 128 DI 10.1007/BF02921352 PG 13 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA JW574 UT WOS:A1992JW57400002 ER PT J AU LEVY, MJ HERNANDEZ, ER ADASHI, EY STILLMAN, RJ ROBERTS, CT LEROITH, D AF LEVY, MJ HERNANDEZ, ER ADASHI, EY STILLMAN, RJ ROBERTS, CT LEROITH, D TI EXPRESSION OF THE INSULIN-LIKE GROWTH-FACTOR (IGF)-I AND (IGF)-II AND THE IGF-I AND IGF-II RECEPTOR GENES DURING POSTNATAL-DEVELOPMENT OF THE RAT OVARY SO ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; SOMATOMEDIN-C; IMMUNOLOGICAL PROPERTIES; BINDING-PROTEIN; GRANULOSA-CELLS; FEMALE RAT; HORMONE; RNA; TISSUES; PUBERTY AB Solution hybridization/RNase protection assays were used to study the developmental expression of the insulin-like growth factor-I (IGF-I), IGF-II, IGF-I receptor, and IGF-II/mannose-6-phosphate receptor genes in the rat ovary between postnatal days 1-80. Maximal IGF-I mRNA levels occurred during the 15- to 25-day postnatal period, and the level on day 20 represented a 9-fold increase over the baseline at earlier and later stages. IGF-II mRNA levels were maximal during the 1- to 5-day postnatal period and subsequently declined to undetectable levels after day 10. IGF-I receptor mRNA levels increased 10-fold to a maximum in the 20- to 25-day postnatal period. This pattern was similar to the developmental pattern of [I-125] IGF-I binding in the ovary. Two apparent peaks of IGF-II/mannose-6-phosphate receptor mRNA levels were seen, on day 20 and between days 50-80. These specific and significant changes in the expression of the genes encoding the IGFs and their receptors suggest a role for the IGF system in postnatal ovarian development. C1 NIDDKD,DIABET BRANCH,BLDG 10,ROOM 8S243,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. GEORGE WASHINGTON UNIV,SCH MED,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20037. NR 39 TC 39 Z9 39 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1992 VL 131 IS 3 BP 1202 EP 1206 DI 10.1210/en.131.3.1202 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JK945 UT WOS:A1992JK94500029 PM 1324154 ER PT J AU ZHOU, J BONDY, C AF ZHOU, J BONDY, C TI INSULIN-LIKE GROWTH FACTOR-II AND ITS BINDING-PROTEINS IN PLACENTAL DEVELOPMENT SO ENDOCRINOLOGY LA English DT Article ID IGF RECEPTOR; EXPRESSION; RAT; LIVER; GENE AB To identify potential mediators or modulators of insulin-like growth factor-II (IGF-II) action in the placenta, we used in situ hybridization to map patterns of gene expression for IGF-II, the functionally related IGF-binding proteins (IGFBPs) 1-4, and the type 1 and 2 IGF receptors in developing rat and term human placentas. IGF-II mRNA was highly abundant in trophoblast-derived elements of the rat placenta from implantation to maturity, except for a significant local reduction in IGF-II gene expression in the junctional zone just before term. IGFBP2 mRNA was barely detected during early placental development, but increased significantly toward term and was most abundant in the junctional zone. The basal plate of the term human placenta showed a similar pattern, with a superficial layer of cytotrophoblasts containing IGF-II mRNA anatomically apposed to a deeper layer of cells expressing IGFBP2 mRNA. Placental IGFBP1, -3, and -4 mRNAs were much less abundant than IGFBP2 and were restricted to the yolk Bac and vasculature. Type 1 and 2 IGF receptor mRNAs were abundant and shared the same distribution, together with IGF-II, in the labyrinthine zone. These findings suggest that IGFBP2 may be an important modulator of IGF-II action in placental development. Furthermore, the colocalization of both types of IGF receptor mRNA supports the view that these receptors may compete for IGF-II binding in the placenta. RP ZHOU, J (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 23 TC 102 Z9 104 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1992 VL 131 IS 3 BP 1230 EP 1240 DI 10.1210/en.131.3.1230 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JK945 UT WOS:A1992JK94500033 PM 1380437 ER PT J AU PATCHEV, VK KALOGERAS, KT ZELAZOWSKI, P WILDER, RL CHROUSOS, GP AF PATCHEV, VK KALOGERAS, KT ZELAZOWSKI, P WILDER, RL CHROUSOS, GP TI INCREASED PLASMA-CONCENTRATIONS, HYPOTHALAMIC CONTENT, AND INVITRO RELEASE OF ARGININE VASOPRESSIN IN INFLAMMATORY DISEASE-PRONE, HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE-DEFICIENT LEWIS RATS SO ENDOCRINOLOGY LA English DT Article ID PARVOCELLULAR NEUROSECRETORY NEURONS; WALL INDUCED POLYARTHRITIS; PITUITARY-ADRENAL AXIS; CEREBROSPINAL-FLUID; INDUCED ARTHRITIS; NERVOUS-SYSTEM; SECRETION; OXYTOCIN; CRF; ADRENOCORTICOTROPIN AB The susceptibility of Lewis (LEW/N) rats to severe inflammatory disease has been causally associated with subnormal responsiveness of their hypothalamic CRH-secreting neurons and, consequently, their hypothalamic-pituitary-adrenal axis to several stimulatory neurotransmitters and inflammatory cytokines. In the present study we investigated in this strain the secretory dynamics of another major activator of pituitary ACTH secretion, arginine vasopressin (AVP). To accomplish this, we evaluated the circadian plasma concentrations and circadian and glucocorticoid-induced changes in hypothalamic content and in vitro release of AVP in 8- to 10-week-old female LEW/N rats and compared these measurements to those obtained in parallel from age- and sex-matched histocompatible, inflammatory disease-resistant Fischer (F344/N) rats. Plasma concentrations and hypothalamic content and in vitro release of AVP were significantly elevated in LEW/N compared to F344/N rats in both the morning and evening. These indices of higher AVP secretion in LEW/N than in F344/N rats were also present after chronic dexamethasone treatment. These findings suggest increased AVP production and release in LEW/N rats, perhaps representing an adaptive compensation for insufficient CRH and glucocorticoid secretion. The high levels of circulating AVP might contribute to the excessive inflammatory responses of these animals. C1 NIAMSD,ARTHRITIS & RHEUMAT BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP PATCHEV, VK (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N240,BETHESDA,MD 20892, USA. NR 32 TC 45 Z9 45 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1992 VL 131 IS 3 BP 1453 EP 1457 DI 10.1210/en.131.3.1453 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JK945 UT WOS:A1992JK94500061 PM 1505475 ER PT J AU WALMER, DK WRONA, MA HUGHES, CL NELSON, KG AF WALMER, DK WRONA, MA HUGHES, CL NELSON, KG TI LACTOFERRIN EXPRESSION IN THE MOUSE REPRODUCTIVE-TRACT DURING THE NATURAL ESTROUS-CYCLE - CORRELATION WITH CIRCULATING ESTRADIOL AND PROGESTERONE SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR; GENE-EXPRESSION; MESSENGER-RNA; ADHESION; CELLS; LACTOTRANSFERRIN; LOCALIZATION; MOLECULES; PROTEINS; MEMBRANE AB Lactoferrin (LTF), an iron-binding glycoprotein present in most exocrine secretions and in the secondary granules of polymorphonuclear leucocytes (PMN), is regulated by estrogen in the mouse reproductive tract. We investigated the expression of LTF mRNA and protein during the natural estrous cycle to increase our understanding of how this uterine secretory protein is regulated under physiological conditions. There was a positive correlation between LTF mRNA expression in the genital tract and serum estradiol (E2) concentrations. When E2 peaked in proestrus, LTF mRNA and protein were expressed in the uterus; however, during metestrus, when both E2 and progesterone levels were high, LTF mRNA was expressed, while LTF protein was decreasing. LTF protein expression may be hindered by progesterone or some other local factor in the endometrial epithelium after ovulation. Immunohistochemistry demonstrated two distinct staining patterns for LTF in the vaginal and endometrial epithelium. In one staining pattern, the colorimetric reaction was noted over the cytoplasm, and in the other, the nuclear region stained more intensely. This suggests the possibility that in addition to its known role as a secretory protein, LTF may be transported to the nucleus, serving an autocrine role. Our results also indicated that LTF protein is a useful marker for tracking PMN. Nonproliferating epithelial cells in the vagina and endometrium may synthesize chemotactic and/or adhesion molecules for PMN. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP WALMER, DK (reprint author), DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,BOX 3143,DURHAM,NC 27710, USA. NR 39 TC 145 Z9 148 U1 1 U2 7 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1992 VL 131 IS 3 BP 1458 EP 1466 DI 10.1210/en.131.3.1458 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JK945 UT WOS:A1992JK94500063 PM 1505477 ER PT J AU CULLER, MD AF CULLER, MD TI INVIVO EVIDENCE THAT INHIBIN IS A GONADOTROPIN SURGE-INHIBITING ATTENUATING FACTOR SO ENDOCRINOLOGY LA English DT Note ID HUMAN FOLLICULAR-FLUID; SELF-PRIMING ACTION; ENDOGENOUS INHIBIN; STIMULATING-HORMONE; NONSTEROIDAL FACTOR; RAT; LHRH; FSH; RADIOIMMUNOASSAY; IDENTIFICATION AB Hyperstimulation of ovarian function through exogenous gonadotropin administration suppresses the preovulatory surges of both LH and FSH. This phenomenon has been demonstrated to be the result of a non-steroidal factor released from the ovary that has been designated as either gonadotropin surge-inhibiting factor or attenuating factor (GnSIF/AF). To examine the possibility that inhibin might possess the activity ascribed to this factor, endogenous inhibin was immunoneutralized in female rats under conditions known to stimulate GnSIF/AF activity. Inhibin-like immunoreactivity was found to be significantly elevated in FSH-treated fats prior to the time of the gonadotropin surges. Spontaneous preovulatory surges of both LH and FSH were observed in saline-treated (control) rats that were subsequently treated with either anti-inhibin serum (AS) or normal sheep serum (NS). FSH-treatment completely prevented the occurrence of gonadotropin surges in rats subsequently treated with NS. In FSH-injected rats subsequently treated with AS, however, normal preovulatory surges of both LH and FSH were observed. These results indicate that inhibin may be the factor responsible for the suppression of the preovulatory gonadotropin surges in FSH-treated rats and, at least in this species, may be a GnSIF/AF. RP CULLER, MD (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 30 Z9 30 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1992 VL 131 IS 3 BP 1556 EP 1558 DI 10.1210/en.131.3.1556 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JK945 UT WOS:A1992JK94500075 PM 1505482 ER PT J AU DONOSO, AO LOPEZ, FJ NEGROVILAR, A AF DONOSO, AO LOPEZ, FJ NEGROVILAR, A TI CROSS-TALK BETWEEN EXCITATORY AND INHIBITORY AMINO-ACIDS IN THE REGULATION OF LUTEINIZING-HORMONE-RELEASING HORMONE-SECRETION SO ENDOCRINOLOGY LA English DT Note ID N-METHYL-D; RECEPTOR SUBTYPES; ASPARTIC ACID; GABA RELEASE; RAT; GLUTAMATE; NEURONS; TRANSMISSION; STIMULATION; PHACLOFEN AB Inhibitory (IAA) and excitatory amino acid (EAA) neurotransmitters appear to play an important role in regulating reproductive functions. L-Glutamic acid (GLU), the major representative of the EAA system, stimulates LHRH release from arcuate nucleus-median eminence (AN-ME) fragments in vitro. Several studies have provided evidence for considering gamma-aminobutyric acid (GABA) , a major IAA neurotransmitter, as another regulator of LHRH secretion. Recent reports have indicated that a cross-talk between GABA and GLU participates in the regulation of synaptic transmission in the brain. In concert with this notion, we present evidence indicating that this cross-talk between GABA and GLU appears to be also involved in neuroendocrinological paradigms. In this respect, bicuculline, a GABA-A receptor antagonist, blocked GLU-evoked LHRH secretion from AN-ME fragments in vitro without affecting basal LHRH release. In addition, activation of GABA-A receptors by muscimol (MUS) stimulated basal LHRH secretion. Interestingly, when MUS and GLU were added together to the incubation medium, an additive, stimulatory effect was observed. These observations clearly indicate that a GABAergic mechanism participates, via GABA-A receptors, in GLU-induced LHRH secretion from terminals of the ME. Furthermore, GABA-B receptors appear to negatively modulate the effects of GLU. Activation of GABA-B receptors by baclofen (BAC) blocked GLU-induced LHRH secretion, while phaclofen, a GABA-B receptor antagonist, reversed this effect. In summary, our data provide evidence for a cross-talk between EAA and IAA systems in the regulation of LHRH release, and, therefore, in the control of gonadal function. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709. NR 25 TC 68 Z9 68 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1992 VL 131 IS 3 BP 1559 EP 1561 DI 10.1210/en.131.3.1559 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JK945 UT WOS:A1992JK94500076 PM 1354606 ER PT J AU ORTMANN, O STOJILKOVIC, SS CESNJAJ, M EMONS, G CATT, KJ AF ORTMANN, O STOJILKOVIC, SS CESNJAJ, M EMONS, G CATT, KJ TI MODULATION OF CYTOPLASMIC CALCIUM SIGNALING IN RAT PITUITARY GONADOTROPHS BY ESTRADIOL AND PROGESTERONE SO ENDOCRINOLOGY LA English DT Note ID LUTEINIZING-HORMONE SECRETION; PROTEIN-KINASE-C; ANTERIOR-PITUITARY; CELLS; RELEASE; CULTURE; RECEPTORS AB The stimulatory action of GnRH on gonadotropin secretion from cultured rat pituitary cells is modulated by estradiol (E) and progesterone (P). Since secretory responses to GnRH are initiated by phosphoinositide hydrolysis and Ca2+ mobilization, the effects of gonadal steroids on the pattern of Ca2+ signaling were analyzed in single pituitary gonadotrophs. Increasing concentrations of GnRH elicited a spectrum of [Ca2+]i signals in single gonadotrophs, ranging from subthreshold to threshold-oscillatory and biphasic (spike & plateau) responses. In E-treated gonadotrophs, short-term P treatment shifted subthreshold [Ca2+]i responses to oscillatory and oscillatory to biphasic responses, whereas long-term P treatment shifted oscillatory to subthreshold [Ca2+]i response profiles. These changes parallel the effects of P on GnRH-induced LH release, and indicate that the modulatory effects of ovarian steroids on gonadotropin secretion. include a significant action on the Ca2+ signaling pathway. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 10,ROOM B1-L400,BETHESDA,MD 20982. UNIV MARBURG,DEPT OBSTET & GYNECOL,W-3550 MARBURG,GERMANY. NR 21 TC 39 Z9 39 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1992 VL 131 IS 3 BP 1565 EP 1567 DI 10.1210/en.131.3.1565 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JK945 UT WOS:A1992JK94500078 PM 1505483 ER PT J AU EASTMAN, RC GORDEN, P GLATSTEIN, E ROTH, J AF EASTMAN, RC GORDEN, P GLATSTEIN, E ROTH, J TI RADIATION-THERAPY OF ACROMEGALY SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID CONVENTIONAL PITUITARY IRRADIATION; CENTRAL-NERVOUS-SYSTEM; GROWTH-HORMONE; TUMORS; RADIOTHERAPY; HYPOPITUITARISM; COMPLICATIONS; ADENOMAS; FRACTIONATION; RADIONECROSIS C1 NIDDKD, DIABET BRANCH, BETHESDA, MD USA. NCI, RADIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, SCH MED, DIV GERIATR MED & GERONTOL, BALTIMORE, MD 21218 USA. NR 78 TC 94 Z9 97 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 EI 1558-4410 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1992 VL 21 IS 3 BP 693 EP 712 PG 20 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LA542 UT WOS:A1992LA54200012 PM 1521519 ER PT J AU WOLACH, B GOTFRIED, M JEDEIKIN, A LISHNER, M BROSSI, A RAVID, M AF WOLACH, B GOTFRIED, M JEDEIKIN, A LISHNER, M BROSSI, A RAVID, M TI COLCHICINE ANALOGS - EFFECT ON AMYLOIDOGENESIS IN A MURINE MODEL AND, INVITRO, ON POLYMORPHONUCLEAR LEUKOCYTES SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AMYLOIDOSIS; COLCHICINE; 3-DIMETHYLTHIOCOLCHICINE ID PRIMARY BILIARY-CIRRHOSIS AB Colchicine has been used in diverse clinical settings such as gout, familial Mediterranean fever, liver cirrhosis, Behcet's disease and pericarditis. It also has an antimitotic potential hitherto unexplored due to its narrow therapeutic toxic ratio. The aim of the present study was to compare the effectiveness and the toxicity of colchicine and three analogues: thiocolchicine, 2,3 dimethyl-colchicine and 3-dimethylthiocolchicine in the blockage of amyloid synthesis in a murine model. 3-demethylthiocolchicine was equipotent to colchicine in the blockage of casein induced amyloidogenesis. However, it was markedly less toxic (LD50 11.3 mg kg-1 vs. 1.6 mg kg-1). Thiocolchicine was toxic (LD50 1.0 mg kg-1)and 2,3 didemethyl-colchicine was far less effective. The effect of 3-dimethylthiocolchicine on polymorphonuclear leukocytes was then compared to colchicine. The effect of this analogue on inhibition of chemotaxis was equivalent to that of colchicine whereas the latter was superior to the analogue in the suppression of phagocytosis (by a ratio of 2:1) and in the inhibition of bactericidal activity (by a ratio of 10:1). Since in therapeutic concentrations the only detectable effect of colchicine on PMNs is inhibition of chemotaxis, our data may point to 3-demethylthiocolchicine as an optional, perhaps superior alternative to colchicine for some of its therapeutic indications. C1 TEL AVIV UNIV,SACKLER FAC MED,DEPT MED,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,SACKLER FAC MED,DEPT PEDIAT,IL-69978 TEL AVIV,ISRAEL. NIDDK,MED CHEM LAB,BETHESDA,MD. NR 20 TC 9 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD SEP PY 1992 VL 22 IS 9 BP 630 EP 634 DI 10.1111/j.1365-2362.1992.tb01516.x PG 5 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA JN648 UT WOS:A1992JN64800009 PM 1459179 ER PT J AU WOLFEL, C HEINRICHHIRSCH, B SCHULZSCHALGE, T SEIDEL, A FRANK, H RAMP, U WACHTER, F WIEBEL, FJ GONZALEZ, F GREIM, H DOEHMER, J AF WOLFEL, C HEINRICHHIRSCH, B SCHULZSCHALGE, T SEIDEL, A FRANK, H RAMP, U WACHTER, F WIEBEL, FJ GONZALEZ, F GREIM, H DOEHMER, J TI GENETICALLY ENGINEERED V79 CHINESE-HAMSTER CELLS FOR STABLE EXPRESSION OF HUMAN CYTOCHROME-P450IA2 SO EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION LA English DT Article DE HETEROLOGOUS EXPRESSION; CYTOCHROME-P450IA2 (HUMAN); CYP1A2 RECOMBINANT EXPRESSION VECTOR; V79 CHINESE HAMSTER CELLS; P450-DEPENDENT ENZYMATIC ACTIVITY ID SUBSTRATE-SPECIFICITY; METABOLIC-ACTIVATION; MAMMALIAN-CELLS; CDNA; GENE; TRANSFECTION; AFLATOXIN-B1; CARCINOGENS; MUTAGENESIS; LIVER AB V79 Chinese hamster cells were genetically engineered for stable expression of human P450IA2. Full length cDNA, encoding human P450IA2, was inserted into an SV40 early promoter containing eukaryotic expression vector and cointroduced with the selection marker neomycin phosphotransferase (conferring resistance to the neomycin derivative G418) into V79 Chinese hamster cells. The recombinant expression vector was introduced into two different V79 sublines, one expressing an endogenous acetyltransferase (V79-NH), the other not (V79-MZ). The presence of human cytochrome CYP1A2 cDNA in the G418 resistant V79 cell clones was confirmed by Southern blotting. The transcription of the cDNA into mRNA was detected by Northern blotting and the translation into an authentic cytochrome P450IA2 protein was shown by Western blotting. The enzymatic activity in these cells was determined by the cytochrome P450IA2-dependent methoxy-, ethoxy-, benzoxy-, and pentoxyresorufin dealkylation activity. C1 TECH UNIV MUNICH,INST TOXIKOL & UMWELTHYG,LAZARETTSTR 62,W-8000 MUNICH 19,GERMANY. UNIV MAINZ,INST TOXIKOL,W-6500 MAINZ,GERMANY. UNIV MAINZ,INST PATHOL,W-6500 MAINZ,GERMANY. FREE UNIV BERLIN,INST TOXIKOL & EMBRYOPHARMAKOL,W-1000 BERLIN 33,GERMANY. CIBA GEIGY AG,DEPT DRUG SAFETY,CH-4002 BASEL,SWITZERLAND. GESELL STRAHLEN & UMWELTFORSCH MBH,FORSCHUNGSZENTRUM,INST TOXIKOL,W-8042 NEUHERBERG,GERMANY. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. TECH UNIV MUNICH,INST TOXIKOL & UMWELTHYG,W-8000 MUNICH 2,GERMANY. NR 35 TC 46 Z9 46 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6917 J9 EUR J PHARM-ENVIRON JI Eur. J. Pharmacol.-Environ. Toxicol. Pharmacol. Sect. PD SEP 1 PY 1992 VL 228 IS 2-3 BP 95 EP 102 DI 10.1016/0926-6917(92)90017-7 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA JT673 UT WOS:A1992JT67300003 PM 1446722 ER PT J AU MURATA, M GUSOVSKY, F YASUMOTO, T DALY, JW AF MURATA, M GUSOVSKY, F YASUMOTO, T DALY, JW TI SELECTIVE STIMULATION OF CA-2+ FLUX IN CELLS BY MAITOTOXIN SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE MAITOTOXIN; CA-2+ CHANNELS; CATION BLOCKERS; LIPOSOMES ID PHOSPHOINOSITIDE BREAKDOWN; CALCIUM CHANNELS; GUINEA-PIG; SYNAPTOSOMES; RELEASE; ENTRY AB Maitotoxin elicits a dose-dependent stimulation of Ca-45(2+) influx in glioma C6, pheochromocytoma PC12, insulinoma HIT and human blood cells, while having no effect in liposomes. In HIT cells maitotoxin also elicited influx of Rb-86+ > Na-22+ > Mn-54(2+), but the stimulation was far less than for Ca-45(2+). Stimulation of Ca-45(2+) influx was blocked by Ni2+, Co2+, Cd2+ and Mn2+, and markedly reduced by Ba2+. Divalent cations, in particular Ca2+, Ba2+, Mn2+ and Cd2+, enhanced influx of the monovalent cations Na-22+ and Rb-86+. C1 NIDDK,BIOORG CHEM LAB,BLDG 8,RM 1A-15,BETHESDA,MD 20892. TOHOKU UNIV,FAC AGR,FOOD HYG LAB,SENDAI 981,JAPAN. OI murata, michio/0000-0002-1600-145X NR 19 TC 36 Z9 37 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD SEP 1 PY 1992 VL 227 IS 1 BP 43 EP 49 DI 10.1016/0922-4106(92)90140-Q PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JK943 UT WOS:A1992JK94300005 PM 1330638 ER PT J AU BASILE, AS PAUL, IA DECOSTA, B AF BASILE, AS PAUL, IA DECOSTA, B TI DIFFERENTIAL-EFFECTS OF CYTOCHROME-P-450 INDUCTION ON LIGAND-BINDING TO DELTA-RECEPTORS SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Note DE CYTOCHROME P-450; DELTA-RECEPTORS; PHENOBARBITAL; 3-METHYLCHOLANTHRENE ID SIGMA; BRAIN; SITES AB The identity of the sigma-receptor as a form of cytochrome P-450 was investigated in rats treated with 3-methylcholanthrene or phenobarbital. The density of [H-3]N,N'-di(o-tolyl)guanidine (DTG) binding to sigma-2 receptors in hepatic subcellular fractions increased following both treatments, while [H-3](+)-pentazocine binding to sigma-1, receptors was unchanged. Furthermore, proadifen and piperonyl butoxide inhibited [H-3](+)-pentazocine and [H-3]DTG binding with low potency. The low affinity of cytochrome P-450 inhibitors for sigma-receptors, the similiar degree of enhancement of [H-3]DTG binding by agents with disparate cytochrome P-450 induction profiles and the lack of change in [H-3](+)-pentazocine binding are inconsistent with the identity of the sigma-receptor as a cytochrome P-450. RP BASILE, AS (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. NR 14 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD SEP 1 PY 1992 VL 227 IS 1 BP 95 EP 98 DI 10.1016/0922-4106(92)90148-O PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JK943 UT WOS:A1992JK94300013 PM 1426026 ER PT J AU LESCH, KP AULAKH, CS WOLOZIN, BL HILL, JL MURPHY, DL AF LESCH, KP AULAKH, CS WOLOZIN, BL HILL, JL MURPHY, DL TI 3-(2-CARBOXYPIPERAZIN-4-YL)PROPYL-1-PHOSPHONIC ACID DECREASES NMDA RECEPTOR MESSENGER-RNA SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Note DE NMDA RECEPTOR MESSENGER RNA; NMDA RECEPTOR ANTAGONISTS; POLYMERASE CHAIN REACTION ID MK-801; BINDING AB Expression of the N-methyl-D-aspartate receptor gene during long-term administration of competitive and non-competitive NMDA antagonists was studied in rat brain using antisense cRNA transcribed from reverse transcriptase-polymerase chain reaction (RT-PCR)-generated rat NMDA receptor cDNA. Unlike non-competitive antagonists, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) markedly decreased NMDA receptor mRNA steady-state concentrations in frontal cortex and hippocampus. Our results are consistent with a regulation of the NMDA receptor at the level of gene expression. C1 NIMH,CTR CLIN,CLIN SCI LAB,CLIN NEUROPHARMACOL SECT,BETHESDA,MD 20892. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 8 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD SEP 1 PY 1992 VL 227 IS 1 BP 109 EP 111 DI 10.1016/0922-4106(92)90151-K PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JK943 UT WOS:A1992JK94300016 PM 1426022 ER PT J AU VUKICEVIC, S KLEINMAN, HK LUYTEN, FP ROBERTS, AB ROCHE, NS REDDI, AH AF VUKICEVIC, S KLEINMAN, HK LUYTEN, FP ROBERTS, AB ROCHE, NS REDDI, AH TI IDENTIFICATION OF MULTIPLE ACTIVE GROWTH-FACTORS IN BASEMENT-MEMBRANE MATRIGEL SUGGESTS CAUTION IN INTERPRETATION OF CELLULAR-ACTIVITY RELATED TO EXTRACELLULAR-MATRIX COMPONENTS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID OSTEOBLAST-LIKE CELLS; LAMININ-A-CHAIN; FACTOR-BETA; INHIBITS PROLIFERATION; BIOLOGICAL-ACTIVITY; PHENOTYPES INVITRO; EMBRYO FIBROBLASTS; DIFFERENTIATION; EXPRESSION; ACTIVATION C1 NIDR,DEV BIOL LAB,CELL BIOL SECT,BLDG 30,ROOM 407,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIDR,BONE CELL BIOL SECT,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 42 TC 366 Z9 372 U1 1 U2 21 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD SEP PY 1992 VL 202 IS 1 BP 1 EP 8 DI 10.1016/0014-4827(92)90397-Q PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA JL089 UT WOS:A1992JL08900001 PM 1511725 ER PT J AU BAKER, GT WILLIAMS, GM AF BAKER, GT WILLIAMS, GM TI PROCEEDINGS OF THE 2ND INTERNATIONAL-CONFERENCE ON LONGEVITY AND AGING - ENVIRONMENTAL AND NUTRITIONAL INFLUENCES ON AGING AND CANCER - PREFACE SO EXPERIMENTAL GERONTOLOGY LA English DT Editorial Material C1 AMER HLTH FDN,VALHALLA,NY 10595. NIA,GERONTOL RES CTR,NATHAN W SHOCK LABS,BALTIMORE,MD 21224. RP BAKER, GT (reprint author), SHOCK AGING RES FDN,14628 CARONA DR,SILVER SPRING,MD 20905, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD SEP-DEC PY 1992 VL 27 IS 5-6 BP 467 EP 468 DI 10.1016/0531-5565(92)90001-G PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA JP128 UT WOS:A1992JP12800001 ER PT J AU WILLIAMS, GM BAKER, GT AF WILLIAMS, GM BAKER, GT TI THE POTENTIAL RELATIONSHIPS BETWEEN AGING AND CANCER SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE AGING; CANCER; COMMON MECHANISMS; ONCOGENES; SUPPRESSOR GENES; CANCER ETIOLOGY ID MICE; CARCINOGENESIS; MUTATIONS; NEOPLASIA; REPAIR AB The potential relationships between aging and cancer have received considerable attention in the scientific literature in recent years. While it is clear that the rates of most types of cancer increase with advancing age and that both the processes of aging and those of cancer are time dependent, an unequivocal relationship between the etiology of cancers and the mechanistic processes of aging has yet to be established. This article discusses the potential causal relationships between the processes of aging and the etiologies of most cancers. C1 SHOCK AGING RES FDN,14628 CARONA DR,SILVER SPRING,MD 20905. AMER HLTH FDN,VALHALLA,NY 10595. NIA,GERONTOL RES CTR,NATHAN W SHOCK LABS,BALTIMORE,MD 21224. NR 42 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD SEP-DEC PY 1992 VL 27 IS 5-6 BP 469 EP 476 DI 10.1016/0531-5565(92)90002-H PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA JP128 UT WOS:A1992JP12800002 PM 1426082 ER PT J AU FLEMING, TP MATSUI, T AARONSON, SA AF FLEMING, TP MATSUI, T AARONSON, SA TI PLATELET-DERIVED GROWTH-FACTOR (PDGF) RECEPTOR ACTIVATION IN CELL-TRANSFORMATION AND HUMAN MALIGNANCY SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE PDGF RECEPTORS; TRANSFORMATION; CANCER ID SIMIAN SARCOMA-VIRUS; ONCOGENE PRODUCT; EXPRESSION; LINE; CARCINOMA; SURAMIN; PROTEIN; CHAINS; GENES AB We demonstrate that the v-sis-transformed NIH/3T3 fibroblasts exhibit tyrosine-phosphorylation of both intracellular and cell surface forms of the alpha and beta platelet-derived growth factor (PDGF) receptors (PDGFRs). Cell proliferation was partially inhibited by PDGF-neutralizing antibody, but was completely blocked by the drug suramin. Suramin treatment markedly reduced tyrosine-phosphorylated cell surface PDGFRs, but had no effect on the tyrosine-phosphorylated intracellular receptor species. These findings indicate that v-sis-activated PDGFRs must attain a cell surface localization to functionally couple with the mitogenic-signaling pathway. Additionally. we were able to demonstrate a functional autocrine loop involving PDGF in human tumor cell lines. Exposure to suramin resulted in diminished receptor autophosphorylation and/or upregulation of the PDGFRs. A subset of the tumor cell lines possessing a PDGF autocrine pathway exhibited a significant reduction in proliferation after exposure to suramin. These findings indicate that a PDGF autocrine loop contributes to the uncontrolled proliferative drive in some human malignancies. C1 KOBE UNIV,SCH MED,DEPT MED,DIV 3,KOBE 650,JAPAN. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP FLEMING, TP (reprint author), WASHINGTON UNIV,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,ST LOUIS,MO 63110, USA. RI Matsui, Toshimitsu/E-8065-2010 NR 21 TC 16 Z9 16 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD SEP-DEC PY 1992 VL 27 IS 5-6 BP 523 EP 532 DI 10.1016/0531-5565(92)90007-M PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA JP128 UT WOS:A1992JP12800007 PM 1385192 ER PT J AU PASSANITI, A ADLER, SH MARTIN, GR AF PASSANITI, A ADLER, SH MARTIN, GR TI NEW MODELS TO DEFINE FACTORS DETERMINING THE GROWTH AND SPREAD OF HUMAN PROSTATE-CANCER SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE PROSTATE CARCINOMA; INVITRO CELL LINES; RECONSTITUTED BASEMENT MEMBRANE; NUDE MICE ID BASEMENT-MEMBRANE; TUMOR-CELLS; LAMININ AB The incidence of many cancers shows a sharp increase with age. This is particularly true of prostate cancer, which arises in many older males. Little or no morbidity is observed as the tumor develops in situ in the prostate. However, once malignant cells escape from the primary lesion and metastasize, the disease assumes a much more serious course. Here we report on the activity of human prostate cancer cells in culture as well as their behavior when transplanted into nude mice. In vitro, several lines of prostate carcinoma cells obtained from metastatic lesions were embedded in reconstituted basement membrane proteins (Matrigel) and found to exhibit highly invasive activity as observed with malignant cells from other types of tumors. Also, we report an improved method for obtaining an increased growth of human prostate cancer cells in nude mice by injecting these cells in Matrigel. Since there are no adequate animal models of prostate cancer, the systems described here may prove useful in defining events underlying the development and progression of the tumor cells to malignant status, as well as facilitate the analyses of novel therapeutic agents to prevent the growth and the spread of this cancer. C1 NIA, GERONTOL RES CTR, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 18 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD SEP-DEC PY 1992 VL 27 IS 5-6 BP 559 EP 566 DI 10.1016/0531-5565(92)90010-W PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA JP128 UT WOS:A1992JP12800010 PM 1426088 ER PT J AU STERN, MD LAKATTA, EG AF STERN, MD LAKATTA, EG TI EXCITATION-CONTRACTION COUPLING IN THE HEART - THE STATE OF THE QUESTION SO FASEB JOURNAL LA English DT Article DE EXCITATION-CONTRACTION COUPLING; SARCOPLASMIC RETICULUM; CALCIUM; CHANNELS; HEART ID CARDIAC SARCOPLASMIC-RETICULUM; CALCIUM RELEASE CHANNEL; RYANODINE RECEPTOR; SKELETAL-MUSCLE; VENTRICULAR MYOCYTES; SINGLE-CHANNEL; ADENINE-NUCLEOTIDE; FEET STRUCTURES; ACTIVATION; CA-2+ AB Recent developments have led to great progress toward determining the mechanism by which calcium is released from the sarcoplasmic reticulum in the heart. The data support the notion of calcium-induced calcium release via a calcium-sensitive release channel. Calcium release channels have been isolated and cloned. This situation creates a paradox, as it has also been found that calcium release is smoothly graded and closely-responsive to sarcolemmal membrane potential, properties that would not be expected of calcium-induced calcium release, which has intrinsic positive feedback. There is, therefore, no quantitative understanding of how the properties of the calcium release channel can lead to the macroscopic physiology of the whole cell. This problem could, in principle, be solved by various schemes involving heterogeneity at the ultrastructural level. The simplest of these require only that the sarcolemmal calcium channel be located in close proximity to one or more sarcoplasmic reticulum release channels. Theoretical modeling shows that such arrangements can, in fact, resolve the positive feedback paradox. An agenda is proposed for future studies required in order to reach a specific, quantitative understanding of the functioning of calcium-induced calcium release. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. RP STERN, MD (reprint author), JOHNS HOPKINS MED INST,DIV CARDIOL,592 CARNEGIE BLDG,600 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 44 TC 70 Z9 72 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 1992 VL 6 IS 12 BP 3092 EP 3100 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA JN505 UT WOS:A1992JN50500011 PM 1325933 ER PT J AU POLLARD, HB DHARIWAL, K ADEYEMO, OM MARKEY, CJ CAOHUY, H LEVINE, M MARKEY, S YOUDIM, MBH AF POLLARD, HB DHARIWAL, K ADEYEMO, OM MARKEY, CJ CAOHUY, H LEVINE, M MARKEY, S YOUDIM, MBH TI A PARKINSONIAN SYNDROME INDUCED IN THE GOLDFISH BY THE NEUROTOXIN MPTP SO FASEB JOURNAL LA English DT Article DE CATECHOLAMINES; MPP+; BRAIN; NEURONS; REGENERATION ID 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; MONOAMINE-OXIDASE; DOPAMINERGIC NEUROTOXICITY; TYROSINE-HYDROXYLASE; PRIMATE MODEL; OPTIC-NERVE; BRAIN; NEURONS; DISEASE; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AB Parkinson's disease has been modeled in humans, lower primates, and to a lesser extent in some other vertebrates by administration of the potent neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6 tetra-hydropyridine). The MPTP model has thus drawn considerable attention as a system to search for anti-Parkinson's disease drugs, although the cost and scarcity of primates has limited extensive applications. We now report that a parkinsonian syndrome can be elicited in the common goldfish (Carassius auratus) by a single dose of MPTP. The syndrome is characterized by profound bradykinesia (slow movement), the full extent of which is reached 3 days after MPTP administration. The reduction in movement is paralleled by loss of dopamine and norepinephrine from the forebrain and mid-brain and in other brain regions as well. The toxic oxidative product of MPTP, MPP+, is also accumulated predominantly in forebrain and midbrain, and pretreatment with the monoamine oxidase blocker tranylcypromine substantially reduces accumulation of the toxic metabolite. A barely perceptible coarseness in balance adjustment also occurs in treated animals. The MPTP-treated goldfish recover normal movement and normal brain monoamine levels within 10-13 days after administration of the drug. We interpret these and other data to indicate that MPTP can induce a Parkinson's disease-like syndrome in the goldfish that is similar in many aspects to the syndrome induced by MPTP in humans and other primates. This remarkable parallel may permit the goldfish to supplement expensive and scarce primates for the purpose of searching and screening neuroprotective drugs with specific relevance to Parkinson's disease. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT NEUROL,BETHESDA,MD 20892. RP POLLARD, HB (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 63 TC 48 Z9 50 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 1992 VL 6 IS 12 BP 3108 EP 3116 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA JN505 UT WOS:A1992JN50500013 PM 1521741 ER PT J AU KARI, FW BUCHER, J EUSTIS, SL HASEMAN, JK HUFF, JE AF KARI, FW BUCHER, J EUSTIS, SL HASEMAN, JK HUFF, JE TI TOXICITY AND CARCINOGENICITY OF HYDROQUINONE IN F344/N RATS AND B6C3F1 MICE SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID BENZENE METABOLITES; STATISTICAL ISSUES; MICRONUCLEI; BINDING; CELLS; COSMETICS; MECHANISM; MOUSE; TESTS AB Toxicology and carcinogenesis studies were conducted by administering hydroquinone (more than 99% pure) by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 wk or 2 yr. 14-day studies were conducted by administering hydroquinone in com oil to rats at doses ranging from 63 to 1000 mg/kg body weight and to mice at doses ranging from 31 to 500 mg/kg, 5 days/wk. In the 13-wk studies, doses for rats and mice ranged from 25 to 400 mg/kg. At those doses showing some indication of toxicity in the 14-day and 13-wk studies, the central nervous system, forestomach and liver were identified as target organs in both species and renal toxicity was observed in rats. Based on these results, 2-yr studies were conducted by administering 0, 25 or 50 mg hydroquinone/kg in deionized water by gavage to groups of 65 rats of each sex, 5 days/wk. Groups of 65 mice of each sex were given 0, 50 or 100 mg/kg on the same schedule. 10 rats and 10 mice from each group were killed and evaluated after 15 months. Mean body weights of high-dose male rats and high-dose mice were approx. 5-14% lower than those of controls during the second half of the study. No differences in survival were observed between dosed and control groups of rats or mice. Nearly all male rats and most female rats in all vehicle control and exposed groups had nephropathy, which was judged to be more severe in high-dose male rats. Hyperplasia of the renal pelvic transitional epithelium and renal cortical cysts were increased in male rats. Tubular cell hyperplasia of the kidney was seen in two high-dose male rats, and renal tubular adenomas were seen in 4/55 low-dose and 8/55 high-dose male rats; none was seen in vehicle controls or in female rats. Mononuclear cell leukaemia in female rats occurred with increased incidences in the dosed groups (vehicle control, 9/55; low dose, 15/55; high dose, 22/55). Compound-related lesions observed in the liver of high-dose male mice included anisokaryosis, syncytial alteration and basophilic foci. The incidences of hepatocellular neoplasms, primarily adenomas, were increased in dosed female mice (3/55; 16/55; 13/55). Follicular cell hyperplasia of the thyroid gland was increased in dosed mice. In summary, there was evidence of hydroquinone-related carcinogenicity in male F344/N rats as indicated by increased incidences of tubular cell adenomas of the kidney, in female rats as shown by increases in mononuclear cell leukaemia, and in female mice based on increases in hepatocellular neoplasms, mainly adenomas. There was no evidence of carcinogenicity in male mice. RP KARI, FW (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 39 TC 55 Z9 58 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD SEP PY 1992 VL 30 IS 9 BP 737 EP 747 DI 10.1016/0278-6915(92)90075-V PG 11 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA JW100 UT WOS:A1992JW10000001 PM 1365401 ER PT J AU JANG, JJ DEVOR, DE LOGSDON, DL WARD, JM AF JANG, JJ DEVOR, DE LOGSDON, DL WARD, JM TI A 4-WEEK FEEDING STUDY OF GROUND RED CHILLI (CAPSICUM-ANNUUM) IN MALE B6C3F1 MICE SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID BALB/C MICE; CAPSAICIN AB The toxicity of red chilli was examined in male B6C3F1 mice fed a commercial meal diet mixed with ground Capsicum annuum (Linn.) at levels of 0.5, 1.0, 2.5, 5.0, 7.5 and 10% by weight. Mice were offered control or test diets ad lib. starting at 6 wk of age. Food consumption was measured daily and individual body weights recorded weekly for the 4-wk feeding period. General health, body weight and food intake were apparently not adversely affected at any level of pepper consumption. Histopathological evaluation revealed slight glycogen depletion and anisocytosis of hepatocytes in the 10% group. However, other organs did not reveal any lesions attributable to the chilli exposure. It appears that red chilli is relatively non-toxic at the doses tested in male B6C3F1 mice. C1 NCI, COMPARAT CARCINOGENESIS LAB, TUMOR PATHOL & PATHOGENESIS SECT, FREDERICK, MD 21702 USA. NCI, PRI DYNCORP, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. RI Jang, JaJune/F-6647-2011 FU NCI NIH HHS [N01-CO-74102] NR 15 TC 16 Z9 16 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD SEP PY 1992 VL 30 IS 9 BP 783 EP + DI 10.1016/0278-6915(92)90080-5 PG 0 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA JW100 UT WOS:A1992JW10000006 PM 1427516 ER PT J AU KIM, H ROSENTHAL, I KIRSCHENBAUM, LJ RIESZ, P AF KIM, H ROSENTHAL, I KIRSCHENBAUM, LJ RIESZ, P TI PHOTOSENSITIZED FORMATION OF ASCORBATE RADICALS BY CHLOROALUMINUM PHTHALOCYANINE TETRASULFONATE - AN ELECTRON-SPIN-RESONANCE STUDY SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE PHTHALOCYANINE; ESR; ASCORBATE RADICALS; PHOTOCHEMISTRY; SINGLET OXYGEN; SUPEROXIDE; FREE RADICALS ID HYDROGEN-PEROXIDE; MOLECULAR-OXYGEN; SINGLET OXYGEN; CYTO-TOXICITY; TRIPLET-STATE; ACID; OXIDATION; SUPEROXIDE; MECHANISM AB The chloroaluminum phthalocyanine tetrasulfonate sensitized photooxidation of ascorbic acid to ascorbate radical (A .-) was followed by electron spin resonance (ESR) spectroscopy. In air saturated aqueous media, steady-state amounts of A .- are rapidly established upon irradiation. The ESR signal disappears within a few seconds after the light is extinguished-more slowly under constant irradiation as oxygen is depleted. No photooxidation was observed in deaerated media. The effect of added superoxide dismutase, catalase, desferrioxamine, and singlet oxygen scavengers (NaN3 and tryptophan) was studied, as was replacement of water by D20 and saturation with O2. The results are indicative of free radical production by direct reaction between ascorbate ion and sensitized phthalocyanine (a Type I mechanism) in competition with the (Type II) reaction of HA- with singlet oxygen, a reaction which does not produce ascorbate radical intermediates. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. AGR RES ORG,VOLCANI CTR,DEPT FOOD SCI,IL-50250 BET DAGAN,ISRAEL. UNIV RHODE ISL,KINGSTON,RI 02881. NR 32 TC 12 Z9 12 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP PY 1992 VL 13 IS 3 BP 231 EP 238 DI 10.1016/0891-5849(92)90019-D PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA JH609 UT WOS:A1992JH60900006 PM 1324204 ER PT J AU RIESZ, P KONDO, T AF RIESZ, P KONDO, T TI FREE-RADICAL FORMATION INDUCED BY ULTRASOUND AND ITS BIOLOGICAL IMPLICATIONS SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE ULTRASOUND; FREE RADICALS; SONOCHEMISTRY; ACOUSTIC CAVITATION; ESR SPIN TRAPPING; POLYMER DEGRADATION; CELL KILLING ID ELECTRON-SPIN-RESONANCE; ISOTOPE-EXCHANGE-REACTIONS; SINGLET OXYGEN PRODUCTION; NON-AQUEOUS LIQUIDS; PULSED ULTRASOUND; ACOUSTIC CAVITATION; HYDROXYL RADICALS; NITROUS-OXIDE; DIAGNOSTIC ULTRASOUND; TRAPPING EVIDENCE AB The chemical effects of ultrasound in aqueous solutions are due to acoustic cavitation, which refers to the formation, growth, and collapse of small gas bubbles in liquids. The very high temperatures (several thousand K) and pressures (several hundred atmospheres) of collapsing gas bubbles lead to the thermal dissociation of water vapor into .OH radicals and .H atoms. Their formation has been confirmed by electron spin resonance (ESR) and spin trapping. The sonochemistry of aqueous solutions of gases and of volatile and nonvolatile solutes is reviewed. The similarities and differences between sonochemistry and radiation chemistry of aqueous solutions are explained. Some unusual characteristics of aqueous sonochemistry can be understood by considering the properties of supercritical water. By the use of rare gases with different thermal conductivities, it is possible to distinguish between temperature-dependent processes such as redox reactions initiated by .OH radicals and .H atoms and pressure-dependent processes which lead to polymer degradation and cell lysis. The evidence for free radical formation in aqueous solutions by pulsed ultrasound is discussed. This subject is of interest because it is related to the possible deleterious effects of ultrasonic diagnostic devices. The role of free radicals and of mechanical effects induced by ultrasound in DNA degradation, inactivation of enzymes, lipid peroxidation, and cell killing is reviewed. C1 FUKUI MED SCH,DEPT EXPTL RADIOL & HLTH PHYS,FUKUI 91011,JAPAN. RP RIESZ, P (reprint author), NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892, USA. NR 197 TC 368 Z9 379 U1 7 U2 78 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP PY 1992 VL 13 IS 3 BP 247 EP 270 DI 10.1016/0891-5849(92)90021-8 PG 24 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA JH609 UT WOS:A1992JH60900008 PM 1324205 ER PT J AU MATON, PN JENSEN, RT AF MATON, PN JENSEN, RT TI USE OF GUT PEPTIDE RECEPTOR AGONISTS AND ANTAGONISTS IN GASTROINTESTINAL-DISEASES SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Review ID SOMATOSTATIN ANALOG SMS-201-995; ZOLLINGER-ELLISON SYNDROME; DOUBLE-BLIND TRIAL; ACUTE VARICEAL HEMORRHAGE; MIGRATING MOTOR COMPLEX; SHORT BOWEL SYNDROME; OCTREOTIDE ACETATE; DUMPING SYNDROME; SMS 201-995; INTRAVENOUS SOMATOSTATIN C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD. RP MATON, PN (reprint author), OKLAHOMA FDN DIGEST RES,711 STANTON L YOUNG BLVD,SUITE 501,OKLAHOMA CITY,OK 73104, USA. NR 105 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 1992 VL 21 IS 3 BP 551 EP 566 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JH606 UT WOS:A1992JH60600004 PM 1355466 ER PT J AU LATIF, F TORY, K MODI, WS GRAZIANO, SL GAMBLE, G DOUGLAS, J HEPPELLPARTON, AC RABBITTS, PH ZBAR, B LERMAN, MI AF LATIF, F TORY, K MODI, WS GRAZIANO, SL GAMBLE, G DOUGLAS, J HEPPELLPARTON, AC RABBITTS, PH ZBAR, B LERMAN, MI TI MOLECULAR CHARACTERIZATION OF A LARGE HOMOZYGOUS DELETION IN THE SMALL-CELL LUNG-CANCER CELL-LINE U2020 - A STRATEGY FOR CLONING THE PUTATIVE TUMOR SUPPRESSOR GENE SO GENES CHROMOSOMES & CANCER LA English DT Article ID INSITU HYBRIDIZATION; LOCALIZATION; CARCINOMA; SEQUENCES; LOCUS; 3P AB Homozygous deletions are instrumental in the detection and cloning of tumor suppressor genes. We report the isolation and characterization of 39 new single-copy probes saturating a submicroscopic homozygous deletion detected in the DNA of the small cell lung cancer (SCLC) cell line U2020. The probes were selected from a large collection, covering the entire length of chromosome 3 with an estimated average spacing of 100-150 kb. Based on the number of probes in the deletion and the probe density, the size of the U2020 submicroscopic deletion was estimated to be in the range of 4-7 megabases. Among the deleted loci, 17 showed conservation across species, probably representing potential coding gene sequences. By genetic and physical mapping of a large randomly chosen fraction of the deleted probes, we defined the location of the U2020 deletion within chromosome band 3p12. Our cloning strategy is based on narrowing the region of interest by eliminating probes that retain heterozygosity in SCLC samples, thus selecting for probes in the region of common loss. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. MRC,CAMBRIDGE CB2 2QH,ENGLAND. PROGRAM RESOURCES INC DYN CORP,FREDERICK,MD. SUNY HLTH SCI CTR,DEPT MED,SYRACUSE,NY. FU NCI NIH HHS [N01-CO-74102] NR 19 TC 45 Z9 45 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 1992 VL 5 IS 2 BP 119 EP 127 DI 10.1002/gcc.2870050205 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA JM782 UT WOS:A1992JM78200004 PM 1381947 ER PT J AU LAZARISKARATZAS, A SMITH, MR FREDERICKSON, RM JARAMILLO, ML LIU, YL KUNG, HF SONENBERG, N AF LAZARISKARATZAS, A SMITH, MR FREDERICKSON, RM JARAMILLO, ML LIU, YL KUNG, HF SONENBERG, N TI RAS MEDIATES TRANSLATION INITIATION FACTOR-4E-INDUCED MALIGNANT TRANSFORMATION SO GENES & DEVELOPMENT LA English DT Article DE EIF-4E; TRANSLATION; SIGNAL TRANSDUCTION; REVERTANTS ID CAP-BINDING PROTEIN; GTPASE-ACTIVATING PROTEIN; MESSENGER-RNA; MONOCLONAL-ANTIBODIES; PHOSPHORYLATION SITE; CELL-PROLIFERATION; PHORBOL ESTERS; FACTORS EIF-4F; GENE FAMILY; FACTOR 4E AB Translation initiation factor eIF-4E binds to the eukaryotic mRNA 5' cap structure (m7GpppN, where N is any nucleotide). eIF-4E is a limiting factor in translation and plays a key role in regulation of translation. We have shown previously that overexpression of eIF-4E in rodent fibroblasts results in tumorigenic transformation. eIF-4E also exhibits mitogenic activity when microinjected into serum-starved NIH-3T3 cells. To understand the mechanisms by which eIF-4E exerts its mitogenic property, we examined the involvement of the Ras signaling pathway in this activity. Here, we report that Ras is activated in eIF-4E-overexpressing cells, as the proportion of GTP-bound Ras is increased. Overexpression of the negative effector of cellular Ras, GTPase activating protein, causes reversion of the transformed phenotype. Furthermore, we show that neutralizing antibodies to Ras, or a dominant-negative mutant of Ras, inhibit the mitogenic activity of eIF-4E. We conclude that eIF-4E exerts its mitogenic and oncogenic activities by the activation of Ras. C1 MCGILL UNIV,DEPT BIOCHEM,MONTREAL H3G 1Y6,QUEBEC,CANADA. MCGILL UNIV,MCGILL CANC CTR,MONTREAL H3G 1Y6,QUEBEC,CANADA. NCI,FREDERICK CANC RES & DEV PROGRAM,DIV CANC TREATMENT,PROGRAM RESOURCES INC,DYNCORP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 58 TC 128 Z9 131 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP PY 1992 VL 6 IS 9 BP 1631 EP 1642 DI 10.1101/gad.6.9.1631 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA JM569 UT WOS:A1992JM56900004 PM 1516827 ER PT J AU ADZUMA, K AF ADZUMA, K TI STABLE SYNAPSIS OF HOMOLOGOUS DNA-MOLECULES MEDIATED BY THE ESCHERICHIA-COLI RECA PROTEIN INVOLVES LOCAL EXCHANGE OF DNA STRANDS SO GENES & DEVELOPMENT LA English DT Article DE HOMOLOGOUS RECOMBINATION; RECA PROTEIN; DNA SYNAPSIS; DNA STRAND EXCHANGE ID GENETIC-RECOMBINATION; ATP HYDROLYSIS; DUPLEX DNA; NUCLEOPROTEIN FILAMENTS; HETERODUPLEX FORMATION; HELICAL FILAMENTS; PARANEMIC JOINTS; BRANCH MIGRATION; 3-STRANDED DNA; TRIPLE HELIX AB Escherichia coli RecA protein promotes stable synapsis between a single-stranded DNA and a homologous duplex DNA, resulting in the formation of a complex of RecA with three DNA strands. To gain insight into the molecular interactions responsible for DNA synapsis, the base-pairing status within the synaptic complex was analyzed by using dimethylsulfate and potassium permanganate as probes. The results indicate that the original base pairs in the parental duplex are disrupted; one strand is displaced and the other strand appears to be involved in Watson-Crick base-pairing with the incoming single-stranded DNA. The state of base-pairing thus resembles that of the end products of strand exchange and not a canonical DNA triple helix involving non-Watson-Crick base-pairing. The results also indicate that this local strand exchange can occur without homology at the ends of the DNA substrates (i.e., when axial rotation of the product heteroduplex with respect to the axis of the parental duplex is obstructed). Taken together, these results suggest that exchange of DNA strands mediated by RecA occur at or before the stage of stable DNA synapsis by a process that does not require DNA rotation. RP ADZUMA, K (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 47 TC 91 Z9 91 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP PY 1992 VL 6 IS 9 BP 1679 EP 1694 DI 10.1101/gad.6.9.1679 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA JM569 UT WOS:A1992JM56900008 PM 1516828 ER PT J AU LEE, YJ WICKNER, RB AF LEE, YJ WICKNER, RB TI MAK10, A GLUCOSE-REPRESSIBLE GENE NECESSARY FOR REPLICATION OF A DSRNA VIRUS OF SACCHAROMYCES-CEREVISIAE, HAS T-CELL RECEPTOR ALPHA SUBUNIT MOTIFS SO GENETICS LA English DT Article ID DOUBLE-STRANDED-RNA; VARIABLE REGION GENES; L-A; KILLER PLASMID; CATABOLITE REPRESSION; INVERTASE SYNTHESIS; MIG1 REPRESSOR; LYMPHOCYTES-T; GAL GENES; YEAST AB The MAK10 gene is necessary for the propagation of the L-A dsRNA virus of the yeast Saccharomyces cerevisiae. We have isolated MAK10 from selected phage-gamma-genomic DNA clones that map near MAK10. This gene encodes a 733-amino acid protein with several regions of similarity to T cell receptor alpha-subunit V (variable) regions. We show that MAK10 is essential for optimal growth on nonfermentable carbon sources independent of its effect on L-A. Although loss of L-A by mak10-1 mutants is partially suppressed by loss of the mitochondrial genome, no such suppression of a mak10=URA3 mutation was observed. Using MAK10-lacZ fusions we show that MAK10 is expressed at a very low level and that it is glucose repressed. The highest levels of expression were seen in tup1 and cyc8 mutants, known to be defective in glucose repression. These results suggest that the mitochondrial genome and L-A dsRNA compete for the MAK10 protein. RP NIDDKD, BIOCHEM PHARMACOL LAB, GENET SIMPLE EUKARYOTES SECT, BETHESDA, MD 20892 USA. NR 70 TC 15 Z9 16 U1 0 U2 0 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD SEP PY 1992 VL 132 IS 1 BP 87 EP 96 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA JK869 UT WOS:A1992JK86900008 PM 1398065 ER PT J AU REED, E JACOB, J OZOLS, RF YOUNG, RC ALLEGRA, C AF REED, E JACOB, J OZOLS, RF YOUNG, RC ALLEGRA, C TI 5-FLUOROURACIL (5-FU) AND LEUCOVORIN IN PLATINUM-REFRACTORY ADVANCED STAGE OVARIAN-CARCINOMA SO GYNECOLOGIC ONCOLOGY LA English DT Article ID ONCOLOGY-GROUP EXPERIENCE; COLORECTAL-CARCINOMA; CANCER; FLUOROURACIL; CISPLATIN; AGENT RP REED, E (reprint author), NIH,MED BRANCH,BLDG 10,ROOM 12N-226,9000 ROCKVILLE PIKE,ROCKVILLE,MD 20892, USA. NR 19 TC 19 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 1992 VL 46 IS 3 BP 326 EP 329 DI 10.1016/0090-8258(92)90226-9 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA JQ941 UT WOS:A1992JQ94100013 PM 1526510 ER PT J AU GOLDMAN, HH MORRISSEY, JP RIDGELY, MS FRANK, RG NEWMAN, SJ KENNEDY, C AF GOLDMAN, HH MORRISSEY, JP RIDGELY, MS FRANK, RG NEWMAN, SJ KENNEDY, C TI LESSONS FROM THE PROGRAM ON CHRONIC MENTAL-ILLNESS SO HEALTH AFFAIRS LA English DT Article ID FOUNDATION PROGRAM; HEALTH AUTHORITIES; JOHNSON,ROBERT,WOOD; REFORM; ILL C1 UNIV N CAROLINA,SOCIAL MED,CHAPEL HILL,NC 27514. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BALTIMORE,MD 21218. NIMH,BETHESDA,MD 20892. RP GOLDMAN, HH (reprint author), UNIV MARYLAND,SCH MED,MENT HLTH POLICY STUDIES PROGRAM,BALTIMORE,MD 21201, USA. NR 25 TC 44 Z9 45 U1 0 U2 0 PU PROJECT HOPE-HEALTH AFFAIRS PI SYRACUSE PA PO BOX 8015, SYRACUSE, NY 13217 SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD FAL PY 1992 VL 11 IS 3 BP 51 EP 68 DI 10.1377/hlthaff.11.3.51 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA JR215 UT WOS:A1992JR21500004 PM 1398453 ER PT J AU WILCOX, ER FEX, J AF WILCOX, ER FEX, J TI CONSTRUCTION OF A CDNA LIBRARY FROM MICRODISSECTED GUINEA-PIG ORGAN OF CORTI SO HEARING RESEARCH LA English DT Note DE GUINEA PIG; ORGAN OF CORTI; MOLECULAR BIOLOGY; CLONING ID EXPRESSION; RNAS; DNA AB Poly (A) RNA was isolated from microdissected guinea pig organ of Corti and converted into cDNA with RNase H- murine leukemia virus reverse transcriptase. After size fractionation, the cDNA was directionally ligated into the vector pSPORT 1 and the plasmids were transformed into DH10B E. coli via electroporation. The library was found to have 3.35 x 10(6) independent colonies with ten percent of the colonies lacking an insert. After checking 33 randomly selected colonies for inserts, the average insert size was 1218 base pairs, ranging from 3300 base pairs to 400 base pairs. The library was screened with a beta-actin oligonucleotide probe and 1.4% of the colonies contained an insert hybridizing to the probe. RP WILCOX, ER (reprint author), NIDCD,MOLEC BIOL LAB,BLDG 36,ROOM 5D-08,BETHESDA,MD 20892, USA. NR 9 TC 31 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD SEP PY 1992 VL 62 IS 1 BP 124 EP 126 DI 10.1016/0378-5955(92)90208-5 PG 3 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA JQ287 UT WOS:A1992JQ28700012 PM 1358871 ER PT J AU DIBISCEGLIE, AM SHINDO, M FONG, TL FRIED, MW SWAIN, MG BERGASA, NV AXIOTIS, CA WAGGONER, JG PARK, Y HOOFNAGLE, JH AF DIBISCEGLIE, AM SHINDO, M FONG, TL FRIED, MW SWAIN, MG BERGASA, NV AXIOTIS, CA WAGGONER, JG PARK, Y HOOFNAGLE, JH TI A PILOT-STUDY OF RIBAVIRIN THERAPY FOR CHRONIC HEPATITIS-C SO HEPATOLOGY LA English DT Article ID NON-B-HEPATITIS; CHRONIC NON-A; ALPHA-INTERFERON; CONTROLLED TRIAL; DOUBLE-BLIND; VIRUS; TRANSFUSION; GENOME AB Interferon-alpha therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and may be associated with intolerable side effects. Ribavirin is a nucleoside analog with a broad spectrum of antiviral action. We conducted an uncontrolled pilot study of ribavirin therapy in 13 patients with chronic hepatitis C. Ribavirin was given for 6 mo, in a dose that was increased, at 2-mo intervals, from 600 mg to 1,000 mg to 1,200 mg/day. Serum ALT levels gradually decreased in all 13 treated patients; the mean percentage of decrease was 67% (from 210 U/L [range = 109 to 5931 to 63 U/L [range = 22 to 108 U/L]; p = 0.0006) after 6 mo of treatment. Serum aminotransferase levels fell to the normal range in four patients (31%). In the 3 to 6 mo after cessation of ribavirin therapy, serum aminotransferase activities gradually rose to near pretreatment levels in all but one patient. Therapy was associated with a significant decrease in the geometric mean titer of hepatitis C virus RNA in serum (1:1,981 vs. 1:199; p < 0.02) although no patients lost hepatitis C virus RNA from serum during therapy. No significant improvement was seen in liver histological appearance. Ribavirin therapy resulted in mild, reversible hemolysis; no patient exhibited symptomatic anemia. These findings suggest that ribavirin has a beneficial effect in patients with chronic hepatitis C, although further studies are needed to determine how ribavirin is best used. C1 NIH,CTR CLIN,OFF DIRECTOR,BETHESDA,MD 20892. RP DIBISCEGLIE, AM (reprint author), NIDDKD,LIVER DIS SECT,BLDG 10,RM 4D 52,BETHESDA,MD 20892, USA. NR 18 TC 240 Z9 241 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1992 VL 16 IS 3 BP 649 EP 654 DI 10.1002/hep.1840160307 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JL739 UT WOS:A1992JL73900006 PM 1505907 ER PT J AU WILCOX, AJ MAXEY, J HERBST, AL AF WILCOX, AJ MAXEY, J HERBST, AL TI PRENATAL DIETHYLSTILBESTROL EXPOSURE AND PERFORMANCE ON COLLEGE ENTRANCE EXAMINATIONS SO HORMONES AND BEHAVIOR LA English DT Article ID SEX-DIFFERENCES; WOMEN; ASSOCIATION; DAUGHTERS; BEHAVIOR; DES C1 AMER COLL TESTING PROGRAM,IOWA CITY,IA 52243. UNIV CHICAGO,DEPT OBSTET & GYNECOL,CHICAGO,IL 60637. RP WILCOX, AJ (reprint author), NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 21 TC 6 Z9 6 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0018-506X J9 HORM BEHAV JI Horm. Behav. PD SEP PY 1992 VL 26 IS 3 BP 433 EP 439 DI 10.1016/0018-506X(92)90012-K PG 7 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA JP561 UT WOS:A1992JP56100012 PM 1398561 ER PT J AU LESHNER, AI AF LESHNER, AI TI A NEW SYSTEM OF CARE FOR THE HOMELESS MENTALLY-ILL SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Editorial Material RP LESHNER, AI (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD SEP PY 1992 VL 43 IS 9 BP 865 EP 865 PG 1 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA JK866 UT WOS:A1992JK86600001 PM 1427692 ER PT J AU BRESLIN, NA AF BRESLIN, NA TI TREATMENT OF SCHIZOPHRENIA - CURRENT PRACTICE AND FUTURE PROMISE SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Article ID NEUROLEPTIC MALIGNANT SYNDROME; INPATIENT FAMILY INTERVENTION; RANDOMIZED CLINICAL-TRIAL; FOLLOW-UP; BEHAVIORAL INTERVENTION; PLASMA-CONCENTRATIONS; COMMUNITY MANAGEMENT; ANTIPSYCHOTIC-DRUGS; CLOZAPINE; SYMPTOMS AB Studies published since 1988 describing the treatment of schizophrenia are reviewed. Antipsychotic agents play a dominant role in treatment, but, except for clozapine, no one drug has been proved more effective than any other. Ineffective medication and medication noncompliance may contribute to apparent treatment resistance. Used in conjunction with drug treatment, supportive psychotherapy that incorporates social skills training appears to be useful. Environmental interventions such as supervised housing and work with families appear to help patients function better in the community and avoid relapse. Trials of new antipsychotic agents and improved understanding of the neurochemistry of schizophrenia offer hope that improved therapies will become available. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. RP BRESLIN, NA (reprint author), GEORGE WASHINGTON UNIV,DEPT PSYCHIAT & BEHAV SCI,2150 PENNSYLVANIA AVE NW,WASHINGTON,DC 20037, USA. NR 64 TC 13 Z9 13 U1 2 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD SEP PY 1992 VL 43 IS 9 BP 877 EP 885 PG 9 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA JK866 UT WOS:A1992JK86600004 PM 1358780 ER PT J AU LATIF, F MODI, WS DUH, FM SCHMIDT, L LI, H GEIL, L ORCUTT, ML HEPPELLPARTON, A RABBITTS, PH LINEHAN, WM ZBAR, B LERMAN, MI AF LATIF, F MODI, WS DUH, FM SCHMIDT, L LI, H GEIL, L ORCUTT, ML HEPPELLPARTON, A RABBITTS, PH LINEHAN, WM ZBAR, B LERMAN, MI TI MOLECULAR AND GENETIC-CHARACTERIZATION AND PHYSICAL MAPPING OF 11 NEW MARKERS DETECTING MULTIALLELE RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISMS ON THE SHORT ARM OF HUMAN CHROMOSOME-3 SO HUMAN GENETICS LA English DT Article ID INSITU HYBRIDIZATION; LINKAGE MAP; DNA; TRANSLOCATIONS; LOCALIZATION; VARIANTS AB Genetic markers with high degrees of polymorphisms are of vital importance in the construction of high resolution (2-4 cM) linkage maps of human chromosomes as specified in the short-term goals of the Human Genome Initiative. In this paper, we report on molecular and genetic characterization and physical localization of 11 new multiallele restriction fragment length polymorphism markers on human chromosome 3p. Ten of these represent three- and four-allele polymorphisms of the base substitution type probably at two adjacent restriction sites. One has been identified as a novel mini-satellite sequence comprising a variable copy number tandem repeat array of a G/T-rich 79-bp sequence. This collection of multiallele polymorphic (PIC values: 0.40-0.60) markers should prove valuable and increase the resolution power of the available chromosome 3p genetic markers. C1 NCI,IMMUNOL LAB,FREDERICK,MD 21702. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. MRC,CLIN ONCOL & RADIOTHERAPEUT UNIT,CAMBRIDGE CB2 2QH,ENGLAND. NCI,SURG BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CO-74102] NR 18 TC 2 Z9 2 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD SEP-OCT PY 1992 VL 90 IS 1-2 BP 17 EP 22 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA JU057 UT WOS:A1992JU05700004 PM 1358787 ER PT J AU ROBINSON, MA AF ROBINSON, MA TI USAGE OF HUMAN T-CELL RECEPTOR V-BETA, J-BETA, C-BETA AND V-ALPHA GENE SEGMENTS IS NOT PROPORTIONAL TO GENE NUMBER SO HUMAN IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; VARIABLE REGION GENES; MAMMARY-TUMOR VIRUS; POSITIVE SELECTION; ANTIGEN RECEPTOR; NEGATIVE SELECTION; CHAIN; EXPRESSION; DELETION; IDENTIFICATION AB Certain T-cell receptor (TCR) beta-chain variable (V), joining (J), and constant (C) gene segments, as well as TCRalpha-chain V gene segments, are disproportionally represented in TCR alpha and beta cDNA libraries derived from PHA-stimulated peripheral blood lymphocytes. Sequences of 138 TCRalpha clones and 96 TCRbeta clones were determined and of these 128 TCRalpha clones and 88 TCRbeta clones were found to contain unique combinations of V, J, and C gene segments or to display diversity in N region nucleotides. The frequency of the V, J, and C genes used in the assembly of unique transcripts was ascertained. Of the 24 reported Vbeta gene families, 21 were observed among the 88 TCRbeta clones including four Vbeta families (Vbeta1, Vbeta2, Vbeta3, and Vbeta4) that were represented in the sample 2 1/2-5 times more frequently than would be expected on the basis of copy number within the gene complex. Seventy-eight percent of the clones were positive for Cbeta2 and more than half of the clones (53%) used one of two Jbeta2 genes: Jbeta2.1 was present in 27 clones and Jbeta2.7 in 20 clones. TCR Valpha families were also disproportionately represented in this sample. Twenty-five of 30 Valpha families were observed in the sample of 128 clones including six recently reported Valpha families. Three Valpha families, Valpha2, Valpha8, and Valpha23, accounted for approximately 40% of the TCRalpha clones and were represented at 18%, 9.4%, and 13.3%, respectively. Both Valpha2 and Valpha8 gene families contain more than one gene; thus the number of clones observed in these families may, in part, be related to gene number. However, Valpha23, which appears to be a single-copy gene family, is significantly overrepresented in this sample. Although disproportional usage of Vbeta genes may be accounted for by superantigen exposure, reasons for disproportional usage of Jbeta, Cbeta, and Valpha genes are presently unknown. RP ROBINSON, MA (reprint author), NIAID,IMMUNOGENET LAB,TWINBROOK FACIL 2,12441 PARKLAWN DR,BETHESDA,MD 20892, USA. NR 39 TC 42 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP PY 1992 VL 35 IS 1 BP 60 EP 67 DI 10.1016/0198-8859(92)90095-5 PG 8 WC Immunology SC Immunology GA KD502 UT WOS:A1992KD50200006 PM 1478894 ER PT J AU GUARCH, R PESCE, C PURAS, A LAZARO, J AF GUARCH, R PESCE, C PURAS, A LAZARO, J TI A QUANTITATIVE APPROACH TO THE CLASSIFICATION OF HYPOSPERMATOGENESIS IN TESTICULAR BIOPSIES FOR INFERTILITY SO HUMAN PATHOLOGY LA English DT Article DE TESTIS; MALE INFERTILITY; BIOPSY; SPERMATOGENESIS ID HUMAN SEMINIFEROUS EPITHELIUM; TESTIS; MEN; VARICOCELE; CELLS C1 NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV SARAGOSSA,DEPT BIOMED & SALUD PUBL,ZARAGOZA,SPAIN. RP GUARCH, R (reprint author), HOSP VIRGEN CAMINO,SERV ANAT PATOL,PAMPLONA,SPAIN. NR 24 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 1992 VL 23 IS 9 BP 1032 EP 1037 DI 10.1016/0046-8177(92)90265-5 PG 6 WC Pathology SC Pathology GA JM795 UT WOS:A1992JM79500010 PM 1516926 ER PT J AU TAUBENBERGER, JK MERINO, MJ MEDEIROS, LJ AF TAUBENBERGER, JK MERINO, MJ MEDEIROS, LJ TI A THYROID BIOPSY WITH HISTOLOGIC FEATURES OF BOTH RIEDELS THYROIDITIS AND THE FIBROSING VARIANT OF HASHIMOTO THYROIDITIS SO HUMAN PATHOLOGY LA English DT Article DE RIEDELS THYROIDITIS; HASHIMOTO THYROIDITIS C1 NCI,DEPT PATHOL,BLDG 10,ROOM 2N212,BETHESDA,MD 20892. NR 14 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 1992 VL 23 IS 9 BP 1072 EP 1075 DI 10.1016/0046-8177(92)90271-4 PG 4 WC Pathology SC Pathology GA JM795 UT WOS:A1992JM79500016 PM 1516929 ER PT J AU SALERNO, JA MURPHY, DGM HORWITZ, B DECARLI, C HAXBY, JV RAPOPORT, SI SCHAPIRO, MB AF SALERNO, JA MURPHY, DGM HORWITZ, B DECARLI, C HAXBY, JV RAPOPORT, SI SCHAPIRO, MB TI BRAIN ATROPHY IN HYPERTENSION - A VOLUMETRIC MAGNETIC-RESONANCE-IMAGING STUDY SO HYPERTENSION LA English DT Article DE BRAIN; MAGNETIC RESONANCE IMAGING; ATROPHY; HYPERTENSION, CHRONIC; BLOOD PRESSURE; CEREBRAL VENTRICLES ID CEREBROVASCULAR RISK-FACTORS; CEREBRAL BLOOD-FLOW; LEFT-VENTRICULAR HYPERTROPHY; WHITE MATTER LESIONS; TARGET ORGAN DAMAGE; SIGNAL ABNORMALITIES; NORMAL INDIVIDUALS; ALZHEIMERS TYPE; LEUKO-ARAIOSIS; DEMENTIA AB To determine whether hypertension, the predominant risk factor for stroke and vascular dementia, is associated with brain atrophy, magnetic resonance imaging (MRI) scans were performed to quantify brain volumes and cerebrospinal fluid spaces. Eighteen otherwise healthy, cognitively normal older hypertensive men (mean+/-SD age, 69+/-8 years, duration of hypertension 10-35 years) and 17 age-matched healthy, normotensive male control subjects were studied in a cross-sectional design. Axial proton-density image slices were analyzed using region-of-interest and segmentation analyses. The hypertensive subjects had significantly larger mean volumes of the right and left lateral ventricles (p<0.05, both absolute volume and volume normalized to intracranial volume) and a significantly smaller normalized mean left hemisphere brain volume (p<0.05) with a trend toward significance for a smaller normalized mean right hemisphere volume (p<0.09). Four hypertensive subjects and one healthy control subject were found to have severe periventricular hyperintensities on T2-weighted MRI images. When data for these subjects were removed from the analyses, the normalized lateral ventricle volumes remained significantly larger in the hypertensive group. Lateral ventricle enlargement was not related to age or use of diuretics in the hypertensive group nor to duration of hypertension between 10 and 24 years. Our findings suggest that long-standing hypertension results in structural changes in the brain. Longitudinal studies will determine whether MRI-associated changes are progressive and if such changes identify hypertensive subjects at increased risk for clinically apparent brain dysfunction. RP SALERNO, JA (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6-C-414,BETHESDA,MD 20892, USA. RI DeCarli, Charles/B-5541-2009 NR 65 TC 143 Z9 145 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1992 VL 20 IS 3 BP 340 EP 348 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JL733 UT WOS:A1992JL73300010 PM 1516953 ER PT J AU ABASSI, ZA KLEIN, H KEISER, HR AF ABASSI, ZA KLEIN, H KEISER, HR TI EFFECT OF NEUTRAL ENDOPEPTIDASE (NEP) AND C-ANF RECEPTORS ON THE PHARMACOKINETICS OF ANF AND URODILATIN SO HYPERTENSION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1992 VL 20 IS 3 BP 404 EP 404 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JL733 UT WOS:A1992JL73300048 ER PT J AU ABASSI, ZA KEISER, HR AF ABASSI, ZA KEISER, HR TI BRADYKININ DOES NOT MODULATE THE NATRIURETIC RESPONSE TO ANF IN RATS WITH HEART-FAILURE SO HYPERTENSION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1992 VL 20 IS 3 BP 426 EP 426 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JL733 UT WOS:A1992JL73300129 ER PT J AU OCONNELL, DP HANNUM, DB SIBLEY, DR FELDER, RA CAREY, RM AF OCONNELL, DP HANNUM, DB SIBLEY, DR FELDER, RA CAREY, RM TI LOCALIZATION OF SPECIFIC DOPAMINE RECEPTOR SUBTYPES IN THE RAT-KIDNEY AND ADRENAL-GLAND SO HYPERTENSION LA English DT Meeting Abstract C1 UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1992 VL 20 IS 3 BP 433 EP 433 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JL733 UT WOS:A1992JL73300160 ER PT J AU FOX, CH COTTLERFOX, M AF FOX, CH COTTLERFOX, M TI THE PATHOBIOLOGY OF HIV-INFECTION SO IMMUNOLOGY TODAY LA English DT Editorial Material ID FOLLICULAR DENDRITIC CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS; COMPLEXES; DISEASE; PLASMA AB The follicular dendritic cells (FDCs) of the germinal center are known to absorb antigens in the form of immune complexes and to express them on the cell surface for long periods of time. Here, Cecil Fox and Michele Cottler-Fox propose that, as a result of FDC binding of immune-complexed viruses, lymphoid organs are the major reservoirs of HIV, and that FDC's play a key role in infection of CD4+ T cells. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP FOX, CH (reprint author), MOLEC HISTOL LABS,7605-F AIRPK RD,GAITHERSBURG,MD 20879, USA. NR 23 TC 53 Z9 53 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD SEP PY 1992 VL 13 IS 9 BP 353 EP 356 DI 10.1016/0167-5699(92)90171-3 PG 4 WC Immunology SC Immunology GA JM222 UT WOS:A1992JM22200007 PM 1361326 ER PT J AU SCHNEERSON, R LEVI, L ROBBINS, JB BRYLA, DM SCHIFFMAN, G LAGERGARD, T AF SCHNEERSON, R LEVI, L ROBBINS, JB BRYLA, DM SCHIFFMAN, G LAGERGARD, T TI SYNTHESIS OF A CONJUGATE VACCINE COMPOSED OF PNEUMOCOCCUS TYPE-14 CAPSULAR POLYSACCHARIDE BOUND TO PERTUSSIS TOXIN SO INFECTION AND IMMUNITY LA English DT Article ID LYMPHOCYTOSIS-PROMOTING FACTOR; BORDETELLA-PERTUSSIS; FILAMENTOUS HEMAGGLUTININ; WHOOPING-COUGH; OTITIS-MEDIA; ANTIBODY-RESPONSE; ADULT VOLUNTEERS; PROTEIN; IMMUNOGENICITY; MICE AB Type 14 is one of the common types isolated from patients of all ages with infections caused by Streptococcus pneumoniae. Its capsular polysaccharide (Pn14) is composed of a neutrally charged tetrasaccharide repeat unit. Pn14 does not elicit protective levels of antibodies in infants and children and is a less than optimal immunogen of the 23-valent vaccine for adults. Pertussis toxin (PT) is both a virulence factor and protective antigen of Bordetella pertussis: it is not soluble at neutral pH and forms insoluble complexes with acidic polysaccharides. Both Pn14 and PT are potential components of vaccines for infants and children. Accordingly, a synthetic scheme was devised to prepare a conjugate of Pn14 and PT. An adipic acid hydrazide derivative of Pn14 was bound to PT at pH 3.9 by carbodiimide-mediated condensation. The conjugation procedure inactivated the PT as assayed by CHO cell and histamine-sensitizing activity. The Pn14-PT conjugate elicited antibodies in mice to Pn14 at levels estimated to be protective in humans and elicited neutralizing antibodies to PT. We plan to evaluate Pn14-PT clinically. C1 NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892. SUNY DOWNSTATE MED CTR,DEPT MICROBIOL & IMMUNOL,BROOKLYN,NY 11203. GOTHENBURG UNIV,DEPT MED MICROBIOL,S-41124 GOTHENBURG,SWEDEN. RP SCHNEERSON, R (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892, USA. NR 41 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1992 VL 60 IS 9 BP 3528 EP 3532 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JJ861 UT WOS:A1992JJ86100010 PM 1500160 ER PT J AU LEE, L ANDERSON, V PIRINGER, P BOONE, J HENDERSON, DK AF LEE, L ANDERSON, V PIRINGER, P BOONE, J HENDERSON, DK TI AN EPIDEMIOLOGIC APPROACH TO QUALITY IMPROVEMENT, QUALITY ASSURANCE, AND CLINICAL RESEARCH SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HOSPITAL EPIDEMIOLOGY; HEALTH-CARE C1 NIH,WARREN G MAGNUSON CLIN CTR,QUAL ASSURANCE SERV,BLDG 10,ROOM 2C146,BETHESDA,MD 20892. NR 21 TC 3 Z9 3 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 1992 VL 13 IS 9 BP 545 EP 552 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA JN691 UT WOS:A1992JN69100013 PM 1431003 ER PT J AU THOMA, GR AF THOMA, GR TI SAA IMAGE-PROCESSING - KILLEN,M SO INFORMATION PROCESSING & MANAGEMENT LA English DT Book Review RP THOMA, GR (reprint author), NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,BETHESDA,MD 20209, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4573 J9 INFORM PROCESS MANAG JI Inf. Process. Manage. PD SEP-OCT PY 1992 VL 28 IS 5 BP 663 EP 664 DI 10.1016/0306-4573(92)90035-X PG 2 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA JQ789 UT WOS:A1992JQ78900010 ER PT J AU ROBEY, EA RAMSDELL, F GORDON, JW MAMALAKI, C KIOUSSIS, D YOUN, HJ GOTTLIEB, PD AXEL, R FOWLKES, BJ AF ROBEY, EA RAMSDELL, F GORDON, JW MAMALAKI, C KIOUSSIS, D YOUN, HJ GOTTLIEB, PD AXEL, R FOWLKES, BJ TI A SELF-REACTIVE T-CELL POPULATION THAT IS NOT SUBJECT TO NEGATIVE SELECTION SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE ANERGY; AUTOIMMUNITY; CD8; CLONAL DELETION; CORECEPTOR; T-CELL ANTIGEN RECEPTOR ID RECEPTOR TRANSGENIC MICE; TOLERANCE INDUCTION; POSITIVE SELECTION; BEARING THYMOCYTES; CLONAL ANERGY; GENE; ANTIGEN; THYMUS; DELETION; INACTIVATION AB In male mice expressing a transgenic alphabeta TCR which recognizes a male antigen (HY), T cells which do not express normal levels of CD8 escape thymic deletion and appear in the periphery. These consist of two distinct populations, one which lacks expression of both CD4 and CD8, and one with low levels of CD8. Neither population has anti-HY reactivity, consistent with the known requirement of this TCR for CD8. We now describe the consequences of expression of both the anti-HY TCR transgene and a constitutive CD8.1 transgene on T cells of male mice. Peripheral T cells in these male 'double transgenic' mice express both the anti-HY TCR and normal levels of CD8, and can proliferate to male antigen in vitro. These cells do not express the endogenous allele of CD8 (CD8.2), suggesting that the increase in CD8 levels due to the CD8.1 transgene leads to the deletion of the CD8.2low population. In contrast, the CD8.1 transgene does not lead to the deletion of the CD8.2- population. This implies that, unlike the majority of alphabeta T cells, TCR+CD4-CD8- cells in TCR transgenic mice are not subject to deletion. C1 COLUMBIA UNIV,DEPT BIOCHEM & MOLEC BIOPHYS,NEW YORK,NY 10032. COLUMBIA UNIV,HOWARD HUGHES MED INST,NEW YORK,NY 10032. NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. CUNY MT SINAI SCH MED,DEPT OBSTET GYNECOL & REPROD SCI,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT BIOCHEM,NEW YORK,NY 10029. NATL INST MED RES,GENE STRUCT & EXPRESS LAB,LONDON NW7 1AA,ENGLAND. UNIV TEXAS,DEPT MICROBIOL,AUSTIN,TX 78712. NR 28 TC 28 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD SEP PY 1992 VL 4 IS 9 BP 969 EP 974 DI 10.1093/intimm/4.9.969 PG 6 WC Immunology SC Immunology GA JP315 UT WOS:A1992JP31500002 PM 1390439 ER PT J AU KRISPIN, O STERNBERG, KJ LAMB, ME AF KRISPIN, O STERNBERG, KJ LAMB, ME TI THE DIMENSIONS OF PEER EVALUATION IN ISRAEL - A CROSS-CULTURAL-PERSPECTIVE SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID UNITED-STATES; AGGRESSIVENESS; ASSERTIVENESS; CHILDREN AB The Revised Class Play (RCP), a procedure designed to assess peer evaluations, was administered to 1445 second-through seventh-grade children in Israel. Recent studies, using North American samples, revealed three reliable dimensions: Sociability-Leadership; Aggressive-Disruptive; and Sensitive-Isolated. The goal of the present study was to see whether the same three dimensions were evident when the RCP was used in Israel. The principal-components analyses revealed interesting degrees of cross-cultural convergence and divergence. The results are discussed in the context of other research on Israeli values. C1 NICHHD,SOCIAL & EMOT DEV SECT,9190 ROCKVILLE PIKE,ROOM 331,BETHESDA,MD 20892. NR 18 TC 27 Z9 27 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD SEP PY 1992 VL 15 IS 3 BP 299 EP 314 PG 16 WC Psychology, Developmental SC Psychology GA JN500 UT WOS:A1992JN50000001 ER PT J AU SPANGRUDE, GJ AF SPANGRUDE, GJ TI CHARACTERISTICS OF THE HEMATOPOIETIC STEM-CELL COMPARTMENT IN ADULT MICE SO INTERNATIONAL JOURNAL OF CELL CLONING LA English DT Review DE HEMATOPOIESIS; HEMATOPOIETIC STEM CELLS; CELL CYCLE; HEMATOPOIETIC ASSAYS; DIFFERENTIATION COMMITMENT ID COLONY-FORMING CELLS; CFU-S CELL; BONE-MARROW; LIMITING-DILUTION; COMPETITIVE REPOPULATION; W/WV MICE; B-CELL; MOUSE; SEPARATION; GROWTH AB Mouse hematopoietic stem cells can be enriched from adult bone marrow by a number of methods. The resulting cell populations are heterogeneous in function, suggesting a complex organizational structure within the stem cell compartment. Several assays can be applied to the study of early stages of hematopoiesis; however clonal assays for long-term repopulation, the most critical operational definition of hematopoietic stem cells, are lacking. Further complicating the prospect of understanding early hematopoiesis is the finding that genetic variations among laboratory strains of mice lead to major differences in phenotypic and functional characteristics of hematopoietic stem cells. Application to the human situation of the methodology developed for stem cell isolation and characterization in the mouse will be hampered by the possibility of genetic variations among human subjects and the lack of a well-characterized assay system to detect and quantify cells capable of long-term repopulation of irradiated recipients. RP SPANGRUDE, GJ (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 52 TC 16 Z9 15 U1 0 U2 0 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 0737-1454 J9 INT J CELL CLONING PD SEP PY 1992 VL 10 IS 5 BP 277 EP 285 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA JP045 UT WOS:A1992JP04500004 PM 1453014 ER PT J AU FABSITZ, RR CARMELLI, D HEWITT, JK AF FABSITZ, RR CARMELLI, D HEWITT, JK TI EVIDENCE FOR INDEPENDENT GENETIC INFLUENCES ON OBESITY IN MIDDLE-AGE SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE TWINS; GENETICS; HERITABILITY; BODY MASS INDEX; BODY WEIGHT; DEVELOPMENT MODEL; LONGITUDINAL STUDIES; HUMANS; ADULTS ID BODY-FAT; ENVIRONMENTAL-INFLUENCES; DEVELOPMENTAL-CHANGE; RISK-FACTORS; WEIGHT; TWINS; CONTINUITY; ADOPTION; DISEASE; FATNESS AB The National Heart, Lung, and Blood Institute (NHLBI) Twin Study provided longitudinal data on a cohort of 514 pairs of adult male twin pairs who were examined at approximate ages of 48, 57, and 63 years. Because the sample was selected from military veterans, height and weight data were also available from their induction physical examinations when they were approximately 20 years of age. From the total NHLBI Twin Study cohort, 124 monozygotic and 119 dizygotic male twin pairs had complete data available for both members of the pair at induction and three examinations spanning 43 years of adult life. Using these data, the contributions of genetics and shared and non-shared environmental factors to BMI over the 43 year period were estimated by model fitting procedures. Model fitting included both a factor decomposition of these effects as well as a developmental path model. Results from the decomposition procedure indicate significant genetic effects at each examination cycle. Fitting a developmental path model, two independent genetic contributions to the variability of BMI were found: one at, or prior to, the induction examination about age 20, and a second between ages 20 and 48. Significant non-shared environmental contributions at each examination were also indicated, but shared environmental effects were not significant. We conclude that cumulative genetic effects explain most of the tracking in obesity over time; non-shared environmental effects, although significant at each age, are relatively short-lived and make only a minor contribution to tracking. C1 SRI INT,MENLO PK,CA 94025. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. RP FABSITZ, RR (reprint author), NHLBI,CLIN & GENET EPIDEMIOL BRANCH,FED BLDG ROOM 3-A-17,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL31010]; NIAAA NIH HHS [AA08672]; NIMH NIH HHS [MH45268] NR 25 TC 84 Z9 86 U1 0 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 1992 VL 16 IS 9 BP 657 EP 666 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA JM651 UT WOS:A1992JM65100006 PM 1328090 ER PT J AU SEIDELL, JC MULLER, DC SORKIN, JD ANDRES, R AF SEIDELL, JC MULLER, DC SORKIN, JD ANDRES, R TI FASTING RESPIRATORY EXCHANGE RATIO AND RESTING METABOLIC-RATE AS PREDICTORS OF WEIGHT-GAIN - THE BALTIMORE LONGITUDINAL-STUDY ON AGING SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE BODY WEIGHT; METABOLIC RATE; RESPIRATORY EXCHANGE RATIO ID INSULIN RESISTANCE; ENERGY-EXPENDITURE; FIBER TYPE; OBESITY; OXIDATION; FAT; DENSITY; WOMEN; MEN AB ne authors followed 775 men (aged 18-98 years) participating in the Baltimore Longitudinal Study in Aging for an average of ten years. Resting metabolic rate and fasting respiratory exchange ratio (RER) were measured by indirect calorimetry on their first visit and related to subsequent weight change. Deviations from the predicted value of resting metabolic rates (predicted from their estimated fat-free mass) were calculated. Average weight change was 0.07 kg (s.d. 6.4 kg); 122 men (15.3%) gained more than 5 kg and 40 (5.2%) more than 10 kg during the follow-up. After adjustment for initial age, body mass index, fat-free mass, and duration of follow-up, RER, but not RMR or deviations from predicted RMR, was positively related to weight change (P < 0.001). Major weight gain (from at least 5 kg to at least 15 kg) was related to initial RER in non-obese men only (initial body mass index <25 kg/m2) . From Cox proportional hazard regression analyses the adjusted relative risk of gaining 5 kg or more in initially non-obese men with a fasting RER of 0.85 or more was calculated to be 2.42 (95% confidence interval: 1.10-5.32) compared to men with a fasting RER less than 0.76. It was concluded that a relatively high fasting RER is a weak but significant predictor of substantial weight gain in non-obese white men. C1 NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,BALTIMORE,MD 21224. RI seidell, jacob/N-7427-2013 NR 19 TC 216 Z9 218 U1 9 U2 19 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 1992 VL 16 IS 9 BP 667 EP 674 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA JM651 UT WOS:A1992JM65100007 PM 1328091 ER PT J AU SAWYER, TK STAPLES, DJ LIU, L TOMASSELLI, AG HUI, JO OCONNELL, K SCHOSTAREZ, H HESTER, JB MOON, J HOWE, WJ SMITH, CW DECAMP, DL CRAIK, CS DUNN, BM LOWTHER, WT HARRIS, J POORMAN, RA WLODAWER, A JASKOLSKI, M HEINRIKSON, RL AF SAWYER, TK STAPLES, DJ LIU, L TOMASSELLI, AG HUI, JO OCONNELL, K SCHOSTAREZ, H HESTER, JB MOON, J HOWE, WJ SMITH, CW DECAMP, DL CRAIK, CS DUNN, BM LOWTHER, WT HARRIS, J POORMAN, RA WLODAWER, A JASKOLSKI, M HEINRIKSON, RL TI HIV PROTEASE (HIV PR) INHIBITOR STRUCTURE-ACTIVITY-SELECTIVITY, AND ACTIVE-SITE MOLECULAR MODELING OF HIGH-AFFINITY LEU-PSI-[CH(OH)CH2]VAL MODIFIED VIRAL AND NONVIRAL SUBSTRATE-ANALOGS SO INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH LA English DT Article DE ENZYME INHIBITION; HUMAN IMMUNODEFICIENCY VIRUS; HIV PROTEASE; MOLECULAR MODELING; PEPSTATIN; PEPTIDOMIMETIC; STRUCTURE-ACTIVITY ID DESIGN; POTENT; SPECIFICITY; MATURATION; PROTEINASE; PEPTIDES AB This report details the structure-activity relationships of the HIV gag substrate analog Val-Ser-Gln-Asn-Leupsi[CH(OH)CH2]Val-Ile-Val(U-85548E), an inhibitor exhibiting subnanomolar affinity towards HIV type-1 aspartic proteinase (HIV-1 PR). Our data show that the P1-P2' tripeptidyl sequence provides the minimal chemical determinant for HIV-1 PR binding. We describe the structure-activity properties of Leupsi[CH(OH)CH2]Val substitution in other peptidyl ligands of nonviral substrate origin (e.g., angiotensinogen, insulin and pepstatin). Furthermore, the aspartic proteinase selectivities of a few key compounds are summarized relative to evaluation against human renin, human pepsin, and the fungal enzyme, rhizopuspepsin. These studies have led to the rational design of nanomolar potent inhibitors of both HIV-1 and HIV-2 PR. Finally, a 2.5 angstrom resolution X-ray crystallographic structure of U-85548E complexed to synthetic HIV-1 PR dimer (Jaskolski et al, Biochemistry 30, 1600 [1991]) provided a 3-D picture of the inhibitor bound to the enzyme active site, and we performed computer-assisted molecular modeling studies to explore the possible binding modes of the above series of Leupsi[CH(OH)CH2]Val substituted HIV-1 PR inhibitors. C1 UPJOHN CO,UPJOHN LABS,KALAMAZOO,MI 49001. NCI,FREDERICK CANC RES & DEV CTR,MACROMOLEC STRUCT LAB,FREDERICK,MD 21701. UNIV FLORIDA,DEPT BIOCHEM & MOLEC BIOL,GAINESVILLE,FL 32611. UNIV CALIF SAN FRANCISCO,DEPT PHARMACEUT CHEM,SAN FRANCISCO,CA 94143. RP SAWYER, TK (reprint author), WARNER LAMBERT PARKE DAVIS CO,PEPTIDE & PEPTIDOMIMENT CHEM,ANN ARBOR,MI 48106, USA. FU NCI NIH HHS [N01-CO-74101]; NIDDK NIH HHS [DK 18865] NR 23 TC 9 Z9 9 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0367-8377 J9 INT J PEPT PROT RES JI Int. J. Pept. Protein Res. PD SEP-OCT PY 1992 VL 40 IS 3-4 BP 274 EP 281 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JX365 UT WOS:A1992JX36500014 PM 1478785 ER PT J AU BEHETS, F BISHAGARA, K DISASI, A LIKIN, S RYDER, RW BROWN, C QUINN, TC AF BEHETS, F BISHAGARA, K DISASI, A LIKIN, S RYDER, RW BROWN, C QUINN, TC TI DIAGNOSIS OF HIV-INFECTION WITH INSTRUMENT-FREE ASSAYS AS AN ALTERNATIVE TO THE ELISA AND WESTERN-BLOT TESTING STRATEGY - AN EVALUATION IN CENTRAL AFRICA SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV; ZAIRE; SERODIAGNOSIS; INSTRUMENT FREE ASSAYS AB The efficiency of an alternative instrument-free testing strategy was evaluated using a membrane-based rapid screening assay (HIVCHEK and its new version HIVCHEK 1 + 2) in serial combination with a particle agglutination assay (SERODIA-HIV). Among 1,054 Zairian individuals at high risk of HIV infection, 573 were Western blot-positive for HIV-1 (54.4%) and none were Western blot-positive for HIV-2. In this group, the sensitivities of the serial combination HIVCHEK plus SERODIA-HIV and HIVCHEK 1 + 2 plus SERODIA-HIV were 98.1 and 98.2%, respectively, and the specificities were 99.6 and 99.5% compared with HIV-1 Western blot. The positive predictive values were 99.6% for HIVCHEK plus SERODIA-HIV and 99.5% for HIVCHEK 1 + 2 plus SERODIA-HIV; the negative predictive values were 97.8 and 97.9%, respectively. Among 1,495 pregnant women, 90 were Western blot-positive for HIV-1 (6.0%), and 54 of 1,510 blood donors were HIV-1 Western blot-positive (3.6%). None were positive for HIV-2. The sensitivities of HIVCHEK plus SERODIA-HIV and HIVCHEK 1 + 2 plus SERODIA-HIV in these groups were 98.6 and 99.3%, respectively, and the specificities were 99.8 and 99.7%. The positive and negative predictive values of HIVCHEK plus SERODIA-HIV were 96.6 and 99.9%, respectively, and they were 94.1 and 99.9%, respectively, for HIVCHEK 1 + 2 plus SERODIA-HIV. These instrument-free testing strategies are efficient alternatives for serodiagnosis of HIV-1 infection, although their cost should be further reduced. C1 PROJET SIDA,KINSHASA,ZAIRE. INST TROP MED,DEPT MICROBIOL,ANTWERP,BELGIUM. CLIN NGALIEMA,KINSHASA,ZAIRE. CTR DIS CONTROL,ATLANTA,GA 30333. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 7 TC 24 Z9 25 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD SEP PY 1992 VL 5 IS 9 BP 878 EP 882 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JJ975 UT WOS:A1992JJ97500005 PM 1512687 ER PT J AU YEH, CK HANDELMAN, B FOX, PC BAUM, BJ AF YEH, CK HANDELMAN, B FOX, PC BAUM, BJ TI FURTHER-STUDIES OF SALIVARY INHIBITION OF HIV-1 INFECTIVITY SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-1; SALIVA; ANTIVIRAL; ATH8 CELL; CYTOPATHY ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; PAROTID-SALIVA; ANTIBODIES; ANTIGEN AB An HIV-1/ATH8-cell cytopathic system was used to characterize the previously reported anti-HIV-1 activity of human saliva. Inhibitory activity was demonstrated by monitoring viable cell counts, HIV-1 p24 core antigen, and reverse transcriptase levels. Nonfiltered whole saliva, sterilized by irradiation, protected the ATH8 cells from HIV-1 infection. When HIV-1/saliva mixtures were filtered following incubation, the quantity of virus was significantly less (approximately 50%) than in HIV-1/media-filtered controls, suggesting that salivary aggregation and/or agglutination may be involved in the inhibitory activity. However, a sufficient number of apparently morphologically intact viral particles were still present in the HIV-1/saliva filtrates to lead to infection. When saliva was filtered prior to incubation with HIV-1, these filtrates showed substantial inhibitory activity, although reduced compared with that of nonprefiltered saliva. We conclude that saliva likely has several means by which to inhibit HIV-1 infectivity. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 21 TC 30 Z9 30 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD SEP PY 1992 VL 5 IS 9 BP 898 EP 903 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JJ975 UT WOS:A1992JJ97500008 PM 1512690 ER PT J AU PURI, A DIMITROV, DS GOLDING, H BLUMENTHAL, R AF PURI, A DIMITROV, DS GOLDING, H BLUMENTHAL, R TI INTERACTIONS OF CD4+ PLASMA-MEMBRANE VESICLES WITH HIV-1 AND HIV-1 ENVELOPE GLYCOPROTEIN-EXPRESSING CELLS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE MEMBRANE FUSION; PLASMA MEMBRANE VESICLES; CD4; HIV-1 ENVELOPE ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT SOLUBLE CD4; AIDS-RELATED COMPLEX; RED-BLOOD-CELLS; T-CELLS; INITIAL-STAGES; INFECTION; FUSION; RETROVIRUS; RECEPTOR AB To study interactions between the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120-gp41) and the receptor in the target membrane, CD4, a new experimental system utilizing CD4-carrying plasma membrane vesicles (CD4 PMVs) was developed. CD4 PMVs were prepared by hypotonic lysis of HeLa cells expressing CD4 after infection with recombinant vaccinia virus containing the CD4 cDNA. The CD4 PMVs carried up to 680 CD4 molecules per vesicle. Their fusion with cells expressing gp120-gp41 after infection with recombinant vaccinia virus was monitored by fluorescence video microscopy by using lipophilic fluorescent dyes. Fluorescence changes as a result of fusion occurred within 30 min at 37-degrees-C, and little fluorescence changes were seen with cells expressing the noncleaved HIV-1 envelope glycoprotein (gp160). The preincubation of CD4 PMVs with HIV-1 reduced its infectivity 10-fold. The CD4 PMVs were more effective in inhibiting syncytia formation than sCD4. These results demonstrate that CD4 PMVs could be used to study the mechanisms of HIV-1 envelope-mediated fusion and have the potential to inactivate HIV-1. C1 NCI,LMMB,MEMBRANE STRUCT & FUNCT SECT,BLDG 10,ROOM 41356,BETHESDA,MD 20892. US FDA,CBER,BETHESDA,MD 20014. NR 38 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD SEP PY 1992 VL 5 IS 9 BP 915 EP 920 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JJ975 UT WOS:A1992JJ97500010 PM 1512692 ER PT J AU INGRAHAM, LJ WENDER, PH AF INGRAHAM, LJ WENDER, PH TI RISK FOR AFFECTIVE-DISORDER AND ALCOHOL AND OTHER DRUG-ABUSE IN THE RELATIVES OF AFFECTIVELY ILL ADOPTEES SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE DEPRESSION; ALCOHOL ABUSE; SUBSTANCE ABUSE; GENETICS ID SEX-DIFFERENCES; DEPRESSION; PSYCHOPATHOLOGY; EPIDEMIOLOGY; DAUGHTERS AB We investigated the risk for substance abuse in the biological relatives of adoptees with affective illness, controlling for potential confounds, and additionally assessed risk by probands' and relatives' gender. Our sample consisted of 67 index adoptees with affective illness, matched control adoptees, and their biological and adoptive relatives. Both affective illness and substance abuse were more common in the biological relatives of affectively ill adoptees than in controls' relatives. Affective illness was more common than substance abuse among female index biological relatives, with the opposite pattern observed among male relatives. C1 UNIV UTAH,DEPT PSYCHIAT,SALT LAKE CITY,UT 84112. RP INGRAHAM, LJ (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,ROOM 4C110,BLDG 10,BETHESDA,MD 20892, USA. NR 17 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 1992 VL 26 IS 1 BP 45 EP 51 DI 10.1016/0165-0327(92)90033-3 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JT517 UT WOS:A1992JT51700006 PM 1430667 ER PT J AU KALINER, MA AF KALINER, MA TI HUMAN NASAL HOST DEFENSE AND SINUSITIS SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT SYMP ON MECHANISMS, DIAGNOSIS, AND TREATMENT OF SINUSITIS IN CHILDREN AND ADULTS CY JAN 24-25, 1992 CL SCOTTSDALE, AZ SP ALLEN & HANBURYS DE HOST DEFENSE; SECRETORY IGA; MUCOUS MEMBRANES; SINUSITIS ID PATHO-PHYSIOLOGY; RHINITIS; SECRETIONS; MUCOSA; BRADYKININ; PROTEIN; PEPTIDE AB Sinusitis is an exceptionally common disorder that affects an estimated 35 million Americans per year. The development of sinusitis requires both the presence of a virulent pathogen and the failure of the local immune system to prevent or effectively combat the infection. Identification of the components of the immune defense system of the upper respiratory tract and the possible areas of dysfunction that predispose to sinusitis may be important steps in the eventual prevention of this common disease. The nasal and sinus passages are lined by respiratory mucous membranes. Recent studies have identified some of the constituents found in mucus and their roles in human health and disease. However, the local immune system of the respiratory mucosa is largely unknown, and its role in sinusitis is conjectural. Nasal secretions include many proteins that serve important functions in local mucosal host defense. Most of these host-defense molecules are synthesized and secreted by serous cells in the submucous glands, and it appears that the serous cell is the resident antimicrobial cell in mucous membranes. Currently data suggest that serous cell secretion is abnormal in patients with recurrent sinusitis and that effective treatment leads to correction of the secretory abnormality along with improvement in sinusitis. RP KALINER, MA (reprint author), NIAID,ALLERG DIS SECT,BLDG 10,ROOM 11C205,BETHESDA,MD 20892, USA. NR 28 TC 48 Z9 48 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 1992 VL 90 IS 3 SU S BP 424 EP 430 DI 10.1016/0091-6749(92)90162-U PN 2 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA JP521 UT WOS:A1992JP52100003 PM 1527331 ER PT J AU RACHELEFSKY, GS POLMAR, SH DRUCE, HM KALINER, MA FURUKAWA, CT SPECTOR, SL RICHARDSON, MA SLAVEN EVANS, RE LUSK, RP SHAPIRO, GG ZINREICH, SJ GWALTNEY, JM WALD, ER AF RACHELEFSKY, GS POLMAR, SH DRUCE, HM KALINER, MA FURUKAWA, CT SPECTOR, SL RICHARDSON, MA SLAVEN EVANS, RE LUSK, RP SHAPIRO, GG ZINREICH, SJ GWALTNEY, JM WALD, ER TI WHAT IS SINUSITIS - GENERAL DISCUSSION SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Discussion C1 CHILDRENS HOSP MED CTR,DIV IMMUNOL,FEGAN 6,300 LONGWOOD AVE,BOSTON,MA 02115. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA 15261. NIAID,ALLERG DIS SECT,BETHESDA,MD 20892. NW ASTHMA & ALLERGY CTR,SEATTLE,WA. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. CHILDRENS HOSP & MED CTR,CTR CYST FIBROSIS,SEATTLE,WA 98105. CHILDRENS HOSP & MED CTR,DIV OTOLARYNGOL,SEATTLE,WA 98105. UNIV WASHINGTON,SCH MED,DEPT PEDIAT,SEATTLE,WA 98195. UNIV WASHINGTON,SCH MED,DEPT OTOLARYNGOL HEAD & NECK SURG,SEATTLE,WA 98195. CHILDRENS MEM HOSP,DIV ALLERGY,CHICAGO,IL 60614. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. WASHINGTON UNIV,ST LOUIS CHILDRENS HOSP,SCH MED,ST LOUIS,MO 63130. JOHNS HOPKINS MED INST,RUSSELL H MORGAN DEPT RADIOL,DIV NEURORADIOL,BALTIMORE,MD 21205. UNIV VIRGINIA,SCH MED,HLTH SCI CTR,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22908. UNIV PITTSBURGH,CHILDRENS HOSP PITTSBURGH,SCH MED,PITTSBURGH,PA 15213. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 1992 VL 90 IS 3 SU S BP 431 EP 432 PN 2 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA JP521 UT WOS:A1992JP52100004 ER PT J AU CASSEDY, JH AF CASSEDY, JH TI TO FOSTER THE SPIRIT OF PROFESSIONALISM - SOUTHERN SCIENTISTS AND STATE ACADEMIES OF SCIENCE - MIDGETTE,NS SO JOURNAL OF AMERICAN HISTORY LA English DT Book Review RP CASSEDY, JH (reprint author), NATL LIB MED,BETHESDA,MD 20209, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ORGANIZATION AMER HISTORIANS PI BLOOMINGTON PA 112 N BRYAN ST, BLOOMINGTON, IN 47408 SN 0021-8723 J9 J AM HIST JI J. Am. Hist. PD SEP PY 1992 VL 79 IS 2 BP 675 EP 675 DI 10.2307/2080116 PG 1 WC History SC History GA JN974 UT WOS:A1992JN97400092 ER PT J AU HUESTIS, MA HENNINGFIELD, JE CONE, EJ AF HUESTIS, MA HENNINGFIELD, JE CONE, EJ TI BLOOD CANNABINOIDS .1. ABSORPTION OF THC AND FORMATION OF 11-OH-THC AND THCCOOH DURING AND AFTER SMOKING MARIJUANA SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID DELTA-9-TETRAHYDROCANNABINOL; PLASMA; TETRAHYDROCANNABINOL; METABOLITES C1 NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224. NR 16 TC 183 Z9 196 U1 2 U2 23 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD SEP-OCT PY 1992 VL 16 IS 5 BP 276 EP 282 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA JN989 UT WOS:A1992JN98900002 PM 1338215 ER PT J AU HUESTIS, MA HENNINGFIELD, JE CONE, EJ AF HUESTIS, MA HENNINGFIELD, JE CONE, EJ TI BLOOD CANNABINOIDS .2. MODELS FOR THE PREDICTION OF TIME OF MARIJUANA EXPOSURE FROM PLASMA-CONCENTRATIONS OF DELTA-9-TETRAHYDROCANNABINOL (THC) AND 11-NOR-9-CARBOXY-DELTA-9-TETRAHYDROCANNABINOL (THCCOOH) SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID METABOLITES; SPECTROMETRY; URINE C1 NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224. NR 22 TC 65 Z9 76 U1 1 U2 14 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD SEP-OCT PY 1992 VL 16 IS 5 BP 283 EP 290 PG 8 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA JN989 UT WOS:A1992JN98900003 PM 1338216 ER PT J AU MARTICH, GD PARKER, MM CUNNION, RE SUFFREDINI, AF AF MARTICH, GD PARKER, MM CUNNION, RE SUFFREDINI, AF TI EFFECTS OF IBUPROFEN AND PENTOXIFYLLINE ON THE CARDIOVASCULAR-RESPONSE OF NORMAL HUMANS TO ENDOTOXIN SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE HEMODYNAMICS; CYTOKINES; PROSTAGLANDIN INHIBITION; PHOSPHODIESTERASE INHIBITION; TUMOR NECROSIS FACTOR; SEPSIS; OXYGEN CONSUMPTION; OXYGEN DELIVERY ID TUMOR-NECROSIS-FACTOR; SEPTIC SHOCK; INHIBITION; METHYLPREDNISOLONE; INTERLEUKIN-1; REVERSES; SEPSIS; STATE; SERUM AB Endotoxin is a major mediator of the life-threatening cardiovascular dysfunction that characterizes Gram-negative sepsis. In animal models of endotoxemia, pretreatment with ibuprofen or pentoxifylline attenuates some of these cardiovascular changes. To evaluate the effects of these agents on the human cardiovascular response to endotoxemia, hemodynamic variables were measured serially in 24 normal subjects who were given intravenous endotoxin. The subjects were randomized to receive oral ibuprofen (n = 9), pentoxifylline (n = 10), or no medication before endotoxin administration (n = 5). The subjects were volume loaded 3-5 h after endotoxin administration, and hemodynamic measurements were reassessed. Core temperature after endotoxin alone or endotoxin-pentoxifylline approached a maximum at 3 h (greater-than-or-equal-to 38.6-degrees-C), while the endotoxin-ibuprofen group remained afebrile. At 3 and 5 h, all three groups had significant increases in heart rate, cardiac index, oxygen delivery, and oxygen consumption, while systemic vascular resistance index decreased significantly from baseline. The oxygen extraction ratio remained unchanged. After volume loading, the left ventricular ejection fraction and left ventricular end-diastolic and end-systolic volume indexes did not differ among the groups. The hyperdynamic cardiovascular response to endotoxin in humans occurs in the absence of fever and is not significantly ameliorated by oral cyclooxygenase or phosphodiesterase inhibition. RP MARTICH, GD (reprint author), NIH,DEPT CRYPTOGAMIE,BETHESDA,MD 20892, USA. NR 29 TC 36 Z9 36 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 1992 VL 73 IS 3 BP 925 EP 931 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA JP517 UT WOS:A1992JP51700022 PM 1400057 ER PT J AU JONES, PG KRAH, R TAFURI, SR WOLFFE, AP AF JONES, PG KRAH, R TAFURI, SR WOLFFE, AP TI DNA GYRASE, CS7.4, AND THE COLD SHOCK RESPONSE IN ESCHERICHIA-COLI SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RNA-POLYMERASE; GENE; TRANSCRIPTION; PROTEINS; IDENTIFICATION; TEMPERATURE; EXPRESSION; INDUCTION; SEQUENCE; BINDING AB We identify the A subunit of DNA gyrase as a cold shock protein whose synthesis is sustained following transfer of exponentially growing cultures of Escherichia coli from 37 to 10-degrees-C. After a lag period in which its synthetic rate declines, synthesis of the A subunit of DNA gyrase increases relative to that of total protein. The duration of the lag period in synthesis and the synthetic rate of the A subunit appear dependent on the synthesis of a rapidly induced cold shock protein, CS7.4. The promoter of the gyrA gene contains specific binding sites for the CS7.4 protein, suggesting that CS7.4 acts at the transcriptional level to facilitate continued A-subunit synthesis. As synthesis of the B subunit of DNA gyrase is also sustained during cold shock, we suggest that an increase in the amount of DNA gyrase per cell might occur, which would potentially adapt the cells for growth at reduced temperatures (10-degrees-C). C1 NICHHD,MOLEC GENET LAB,BLDG 6,ROOM 131,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 24 TC 190 Z9 191 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 1992 VL 174 IS 18 BP 5798 EP 5802 PG 5 WC Microbiology SC Microbiology GA JN264 UT WOS:A1992JN26400005 PM 1325964 ER PT J AU GIEBULTOWICZ, JM JOY, JE AF GIEBULTOWICZ, JM JOY, JE TI ONTOGENY OF THE CIRCADIAN SYSTEM CONTROLLING RELEASE OF SPERM FROM THE INSECT TESTIS SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE CIRCADIAN RHYTHM; CIRCADIAN PACEMAKER; TESTIS; SPERM; GYPSY MOTH AB In the gypsy moth, the release of sperm bundles from the testis into the vas deferens is rhythmic and is controlled by a circadian pacemaker located in the reproductive system. However, in males kept since pupation in constant darkness (DD) and temperature, the release of sperm was arrhythmic. The release of sperm became rhythmic when males were transferred from a light-dark cycle (LD 16:8) to DD 6-7 days after pupation- To further investigate the development of the circadian system during the pupal stage, we exposed DD pupae to a single 8-hr pulse of light or 8-hr pulse of a 4-degrees-C temperature increase on different days after pupation. The pattern of sperm release was determined 5-6 days after the pulse. Males that were exposed to light or temperature pulses 5 days after pupation subsequently showed nonrhythmic sperm release. However, about half of the pupae that received the pulse on day 6 and most of the pupae that received it on day 7 subsequently showed synchronized sperm release. These results suggested that the clock underlying rhythmic release of sperm becomes operational at approximately 6 days after pupation-that is, 2 days prior to initiation of rhythmic sperm release from the testis. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. UNIV MARYLAND,DEPT ZOOL,COLL PK,MD 20742. RP GIEBULTOWICZ, JM (reprint author), USDA,INSECT NEUROBIOL & HORMONE LAB,BLDG 306,ROOM 322,BELTSVILLE,MD 20705, USA. NR 18 TC 12 Z9 13 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD FAL PY 1992 VL 7 IS 3 BP 203 EP 212 DI 10.1177/074873049200700302 PG 10 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA JN163 UT WOS:A1992JN16300002 PM 1421474 ER PT J AU FORMANKAY, JD CLORE, GM STAHL, SJ GRONENBORN, AM AF FORMANKAY, JD CLORE, GM STAHL, SJ GRONENBORN, AM TI 1H AND N-15 RESONANCE ASSIGNMENTS AND SECONDARY STRUCTURE OF THE HUMAN THIOREDOXIN C62A, C69A, C73A MUTANT SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE HUMAN THIOREDOXIN; NONACTIVE SITE CYSTEINE MUTANT; RESONANCE ASSIGNMENT; SECONDARY STRUCTURE; PK OF ACTIVE SITE ID RECOMBINANT HUMAN THIOREDOXIN; ESCHERICHIA-COLI; 3-DIMENSIONAL STRUCTURE; NMR-SPECTROSCOPY; H-1-NMR SPECTRA; REDUCED FORM; PROTEINS; RESOLUTION; EXCHANGE; COSY AB The complete assignment of H-1 and N-15 backbone resonances and near-complete H-1 side-chain resonance assignments have been obtained for the reduced form of a mutant of human thioredoxin (105 residues) in which the three non-active site cysteines have been substituted by alanines: C62A, C69A, C73A. The assignments were made primarily on the basis of three-dimensional N-15-separated nuclear Overhauser and Hartmann-Hahn spectroscopy, in conjunction with two-dimensional homonuclear and heteronuclear correlation experiments. Based on comparisons of short-range and interstrand nuclear Overhauser effects, patterns of amide exchange, and chemical-shift differences, the structure appears essentially unchanged from that of the previously determined solution structure of the native protein [Forman-Kay, J.D. et al. (1991) Biochemistry, 30, 2685-2698]. An assay for thioredoxin shows that the C62A, C69A, C73A mutant retains activity. The assignment of the spectrum for this mutant of human thioredoxin constitutes the basis for future studies aimed at comparing the details of the active-site conformation in the reduced and oxidized forms of the protein. C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. NIH,PROT EXPRESS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 37 TC 20 Z9 20 U1 0 U2 1 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD SEP PY 1992 VL 2 IS 5 BP 431 EP 445 DI 10.1007/BF02192807 PG 15 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA JQ989 UT WOS:A1992JQ98900003 PM 1422155 ER PT J AU BLAKE, PR LEE, B SUMMERS, MF ADAMS, MWW PARK, JB ZHOU, ZH BAX, A AF BLAKE, PR LEE, B SUMMERS, MF ADAMS, MWW PARK, JB ZHOU, ZH BAX, A TI QUANTITATIVE MEASUREMENT OF SMALL THROUGH-HYDROGEN-BOND AND THROUGH-SPACE H-1-CD-113 AND H-1-HG-199 J-COUPLINGS IN METAL-SUBSTITUTED RUBREDOXIN FROM PYROCOCCUS-FURIOSUS SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE J-COUPLING; CD-113; HG-199; RUBREDOXIN; HYDROGEN BONDING ID NMR; SPECTROSCOPY AB A method is described for measurement of small unresolvable heteronuclear J couplings. The method is based on quantitative analysis of a phase-purged heteronuclear spin-echo difference spectrum, and is demonstrated for measuring H-1-Cd-113 and H-1-Hg-199 J couplings in metal-substituted rubredoxin (M(r) approximately 5.4 kDa) from Pyrococcus furiosus. Couplings from cadmium to backbone amide protons that are hydrogen bonded to the Cys-S atoms directly bonded to Cd vary from smaller than 0.3 to 1.8 Hz; a 'through-space' coupling between Cd and the protons of an alanine methyl group was measured to be 0.3 Hz. Couplings to Hg-199 are significantly larger and fall in the 0.4-4 Hz range. C1 UNIV MARYLAND BALTIMORE CTY,DEPT CHEM & BIOCHEM,BALTIMORE,MD 21228. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. UNIV GEORGIA,DEPT BIOCHEM,ATHENS,GA 30602. UNIV GEORGIA,CTR METALLOENZYME STUDIES,ATHENS,GA 30602. RI Lee, Brian/F-8380-2013 OI Lee, Brian/0000-0002-0269-7812 FU NIAID NIH HHS [AI-30917]; NIGMS NIH HHS [GM-42561] NR 13 TC 89 Z9 89 U1 2 U2 7 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD SEP PY 1992 VL 2 IS 5 BP 527 EP 533 DI 10.1007/BF02192814 PG 7 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA JQ989 UT WOS:A1992JQ98900010 PM 1422158 ER PT J AU JINGUSHI, S JOYCE, ME BOLANDER, ME AF JINGUSHI, S JOYCE, ME BOLANDER, ME TI GENETIC EXPRESSION OF EXTRACELLULAR-MATRIX PROTEINS CORRELATES WITH HISTOLOGIC-CHANGES DURING FRACTURE REPAIR SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID ENDOCHONDRAL OSSIFICATION; SKELETAL TISSUES; CARTILAGE; COLLAGEN; LOCALIZATION; OSTEONECTIN AB We characterized gene expression in the reparative callus that formed after fracture of the rat femur. The callus was divided into regions of bone formation (hard callus) and cartilage formation (soft callus), and gene expression was examined separately in each region. Expression of extracellular matrix protein genes varied with the progression of repair and differed between hard and soft calluses. Messenger ribonucleic acids (mRNAs) for osteonectin, alkaline phosphatase, and type I procollagen were detected in the hard callus at maximal levels during endochondral ossification and bone remodeling (day 15) and at 50% maximal levels during intramembranous bone formation (day 7). Messenger RNAs for these proteins in the soft callus were detected at low levels during chondrogenesis (day 9) but increased to 80% of maximal levels with chondrocyte hypertrophy and mineralization of the cartilage matrix (day 13). Messenger RNAs for type II procollagen and proteoglycan core protein were detected at maximal levels in the soft callus during chondrogenesis (day 9). Osteocalcin gene expression was detected in the hard callus during endochondral ossification and remodeling but not during intramembranous bone formation or at any time in the soft callus. Osteonectin mRNA was detected in both the hard and soft callus throughout the entire course of fracture repair. Expression of cartilage and bone-related genes correlated with the temporal sequence of histologic changes, suggesting transcriptional regulation of gene expression during repair. Differences in gene expression between hard and soft callus and in each of these regions as repair progressed suggest local regulation of gene expression during cell differentiation and matrix synthesis. C1 NIH,ORTHOPAED RES UNIT,BETHESDA,MD 20892. NR 19 TC 100 Z9 107 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1992 VL 7 IS 9 BP 1045 EP 1055 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JN951 UT WOS:A1992JN95100006 PM 1414497 ER PT J AU MAUVIEL, A KAHARI, VM KURKINEN, M EVANS, CH UITTO, J AF MAUVIEL, A KAHARI, VM KURKINEN, M EVANS, CH UITTO, J TI LEUKOREGULIN, A T-CELL DERIVED CYTOKINE, UP-REGULATES STROMELYSIN-1 GENE-EXPRESSION IN HUMAN DERMAL FIBROBLASTS - EVIDENCE FOR THE ROLE OF AP-1 IN TRANSCRIPTIONAL ACTIVATION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE LEUKOREGULIN; HUMAN DERMAL FIBROBLASTS; STROMELYSIN; TRANSCRIPTION; T-CELLS ID MESSENGER-RNA; MATRIX METALLOPROTEINASE-3; COLLAGENASE GENES; MAMMALIAN-CELLS; RETINOIC ACID; DNA-BINDING; C-JUN; PROMOTER; PROTEIN; TRANSFORMATION AB Leukoregulin (LR), a product of activated T-cells, has been recently shown to modulate the metabolism of extracellular matrix components in human skin fibroblast cultures (Mauviel et al., J Cell Biol 11 3:1455-1462, 1991). In this study we focused our attention on the effects of LR on the expression of stromelysin-1 gene. This matrix metalloprotease has a broad spectrum of degradative activity and it is also required for maximal activation of interstitial collagenase. Incubation of skin fibroblast cultures with LR resulted in a dose- and time-dependent elevation of stromelysin-1 mRNA levels, the maximum enhancement being up to approximately sevenfold. This effect was abolished by cycloheximide, suggesting a requirement for ongoing protein synthesis. Transient cell transfections with a promoter/reporter gene construct containing 1.3 kb of 5' flanking DNA of the human stromelysin-1 gene linked to the chloramphenicol acetyl transferase (CAT) gene, indicated enhancement of promoter activity by LR. This enhancement was abolished by a single base substitution in the AP-1 binding site of the promoter. Furthermore, gel mobility shift assays demonstrated enhanced AP-1 binding activity in nuclear extracts from cells incubated with LR. However, LR did not alter the activity of a construct containing three AP-1 sequences in front of the thymidine kinase promoter linked to the CAT gene. These results collectively suggest that activation of stromelysin-1 gene expression by LR is mediated by AP-1 regulatory elements which are necessary, but not sufficient, for gene response. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT DERMATOL,BLUEMLE LIFE SCI BLDG,233 S 10TH ST,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON INST MOLEC MED,MOLEC DERMATOL SECT,PHILADELPHIA,PA 19107. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MED,PISCATAWAY,NJ 08854. NCI,DIV CANC ETIOL,BIOL LAB,TUMOR BIOL SECT,BETHESDA,MD 20892. RI MAUVIEL, Alain/F-6251-2013 FU NIAMS NIH HHS [R01-AR41439, T32-AR0751] NR 37 TC 21 Z9 21 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD SEP PY 1992 VL 50 IS 1 BP 53 EP 61 DI 10.1002/jcb.240500110 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JL751 UT WOS:A1992JL75100007 PM 1429874 ER PT J AU SZENTENDREI, T LAZARWESLEY, E NAKANE, T VIRMANI, M KUNOS, G AF SZENTENDREI, T LAZARWESLEY, E NAKANE, T VIRMANI, M KUNOS, G TI SELECTIVE REGULATION OF BETA-2-ADRENERGIC RECEPTOR GENE-EXPRESSION BY INTERLEUKIN-1 IN CULTURED HUMAN LUNG-TUMOR CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID BETA-ADRENERGIC RECEPTORS; MESSENGER-RNA LEVELS; ADENYLATE-CYCLASE; DOWN-REGULATION; NECROSIS-FACTOR; ANTAGONIST; PROTEIN; BINDING; CLONING; GLUCOCORTICOIDS AB The regulation of beta-1- and beta-2-adrenergic receptors (beta-1AR and beta-2AR) and receptor gene expression by interleukin-1-alpha (IL-1-alpha) was studied in cultured A549 human lung adenocarcinoma cells. The density and affinity of beta-1AR and beta-2AR were analyzed by computerized curve fitting of I-125-pindolol binding and its displacement by subtype selective antagonists. Steady state levels of receptor mRNAs were quantified by DNA excess solution hybridization assays. A549 cells in preconfluent cultures had fewer beta-1AR than beta-2AR (beta-1: 1.9 +/- 0.3 vs. beta-2: 4.0 +/- 0.5 fmol/mg protein, means +/- SE), but lost most of their beta-2AR upon reaching confluency (beta-1: 2.7 +/- 0.4, beta-2: 0.8 +/- 0.3 fmol/mg). Incubation of preconfluent cells for 24 hr with 20 pM of human recombinant IL-1-alpha did not modify the density of either of the beta-AR subtypes. Similar incubations of confluent cells increased the density of beta-2AR from 0.8 +/- 0.3 to 4.2 +/- 0.9 fmol/mg, while the density of beta-1AR and the antagonist affinities of both receptors remained unaltered. The IL-1-alpha-induced increase in beta-2AR density in confluent cells was antagonized in a concentration-dependent manner by a recombinant protein antagonist of type I IL-1 receptors (IC50: 0.2 nM). The IL-1-alpha-induced increase in beta-2AR density was preceded by an increase in the steady state level of beta-2AR mRNA, while levels of beta-1AR mRNA remained unchanged. IL-1-alpha increased the stability as well as the rate of transcription of beta-2AR mRNA. These findings demonstrate for the first time that activation of type I IL-1 receptors in A549 cells leads to a cell density-dependent, selective upregulation of beta-2AR, and that the mechanism of this effect involves increased formation and stability of the beta-2AR message. C1 NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,BETHESDA,MD 20892. NR 43 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 1992 VL 152 IS 3 BP 478 EP 485 DI 10.1002/jcp.1041520306 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA JK153 UT WOS:A1992JK15300005 PM 1324243 ER PT J AU LIN, Y CHREST, FJ GABRIELSON, EW AF LIN, Y CHREST, FJ GABRIELSON, EW TI REVERSIBLE G1 ARREST OF A HUMAN LUNG EPITHELIAL-CELL LINE BY STAUROSPORINE SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PROTEIN-KINASE-C; PROMYELOCYTIC LEUKEMIA-CELLS; MURINE MACROPHAGE TUMOR; POTENT INHIBITOR; PHORBOL ESTER; INSULIN-RECEPTOR; DOWN-REGULATION; DNA-SYNTHESIS; PHOSPHORYLATION; DIFFERENTIATION AB Staurosporine, a microbial-derived protein kinase inhibitor, reversibly blocked non-synchronized, replicating cultures of the human lung epithelial cell line EKVX in the G1 phase of cell cycle and inhibited DNA synthesis and cell replication. The mechanism of this cell-cycle arrest in EKVX cells by staurosporine was likely due to inhibition of protein kinase C (PKC) because: 1) dose-dependent inhibition of DNA synthesis occurred at levels of staurosporine that inhibit phosphorylation of PKC substrate, 2) inhibition of DNA synthesis was also seen after treatment with another PKC inhibitor H7, but not by the chemically similar HA1004, which has a relative inhibitory specificity for cAMP-dependent protein kinase, and 3) the DNA synthesis was not inhibited by specific tyrosine kinase inhibitors Genistein and Lavendustin A at concentrations that inhibit tyrosine kinase activity. Removal of staurosporine from cell culture media resulted in a rebound in PKC activity and synchronized DNA synthesis in EKVX cultures. The reversibility of the inhibition was noted even after 5 days of treatment with staurosporine, and DNA synthesis remained synchronized for at least two rounds of cell replication after removal of staurosporine. Flow cytometric analysis confirmed that more than 90% of the cell population was blocked in the G1 phase after cells were treated with staurosporine for 24 h. Agents such as staurosporine may be useful for synchronizing cell populations to study cell-cycle specific biochemical events important for the regulation of cell replication in the EKVX cell line. C1 JOHNS HOPKINS UNIV,SCH MED,CTR ASTHMA & ALLERGY,DEPT PATHOL,BALTIMORE,MD 21224. NIA,GERONTOL RES INST,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. FU NIEHS NIH HHS [ES03505] NR 47 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 1992 VL 152 IS 3 BP 646 EP 653 DI 10.1002/jcp.1041520325 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA JK153 UT WOS:A1992JK15300024 PM 1506420 ER PT J AU SCHMIDT, K LUCIGNANI, G MORESCO, RM RIZZO, G GILARDI, MC MESSA, C COLOMBO, F FAZIO, F SOKOLOFF, L AF SCHMIDT, K LUCIGNANI, G MORESCO, RM RIZZO, G GILARDI, MC MESSA, C COLOMBO, F FAZIO, F SOKOLOFF, L TI ERRORS INTRODUCED BY TISSUE HETEROGENEITY IN ESTIMATION OF LOCAL CEREBRAL GLUCOSE-UTILIZATION WITH CURRENT KINETIC-MODELS OF THE [F-18] FLUORODEOXYGLUCOSE METHOD SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE APPARENT GLUCOSE-6-PHOSPHATASE ACTIVITY; K4-ASTERISK; MODELING; RATE CONSTANT ESTIMATION; RATE CONSTANTS ID POSITRON EMISSION TOMOGRAPHY; BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; METABOLIC-RATE; FLUORODEOXYGLUCOSE METHOD; GRAPHICAL EVALUATION; COMPUTED-TOMOGRAPHY; DEOXYGLUCOSE METHOD; NORMAL VALUES; PET AB The effects of tissue heterogeneity on the estimation of regional cerebral glucose utilization (rCMR(glc)) in normal humans with [F-18]2-fluoro-2-deoxy-D-glucose ([F-18]FDG) and positron emission tomography (PET) were compared with respect to the various kinetic models of the [F-18]FDG method. The kinetic models were conventional homogeneous tissue models of the [F-18]FDG method, with (4K Model) and without (3K Model) a rate constant to account for an apparent loss of [F-18]2-fluoro-2-deoxy-D-glucose-6-phosphate ([F-18]FDG-6-P), and a tissue heterogeneity model (TH Model). When either of the kinetic models designed for homogeneous tissues was applied to heterogeneous tissues, estimates of the rate constant for efflux of [F-18] FDG from the tissue (k2*) and of the rate constant for phosphorylation of [F-18]FDG (k3*) decreased as the duration of the experimental period was increased. When the 4K Model was used, estimates of the rate constant for the apparent dephosphorylation of [F-18]FDG-6-P (k4*) were significantly greater than zero and fell with increasing duration of the experimental period. Although the TH Model included no term to describe an apparent dephosphorylation of [F-18]FDG-6-P, the fit of the TH Model to the time course of total tissue radioactivity was at least as good as and often better than the fit of the 4K Model in the 120-min period following the pulse of [F-18]FDG. Hence, the high estimates of k4* found in PET studies of less-than-or-equal-to 120 min can be explained as the consequence of measuring radioactivity in a heterogeneous tissue and applying a model designed for a homogeneous tissue; there remains no evidence of significant dephosphorylation of [F-18]FDG-6-P in this time period. Furthermore, use of the 4K Model led to an overestimation of rCMR(glc); whole-brain glucose utilization calculated with the 4K Model was >20% higher than values usually obtained in normal humans by the model-independent Kety-Schmidt technique. rCMR(glc) was accurately estimated by the TH Model and, in experimental periods sufficiently long to minimize the effects of tissue heterogeneity, also by the original 3K Model of the deoxyglucose method. C1 UNIV MILAN,INST H SAN RAFFAELE,DEPT MED,CNR,IST NEUROSCI & BIOIMMAGINI,I-20122 MILAN,ITALY. RP SCHMIDT, K (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,RM 1A-05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Lucignani, Giovanni/C-6773-2008 NR 31 TC 59 Z9 59 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 1992 VL 12 IS 5 BP 823 EP 834 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA JJ648 UT WOS:A1992JJ64800014 PM 1506447 ER PT J AU MILNE, GWA AF MILNE, GWA TI DRAWPERFECT AND CORELDRAW SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Software Review RP MILNE, GWA (reprint author), NCI,MED CHEM LAB,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD SEP-OCT PY 1992 VL 32 IS 5 BP 570 EP 571 DI 10.1021/ci00009a603 PG 2 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA JQ760 UT WOS:A1992JQ76000028 PM 1400665 ER PT J AU PALKOVITS, M MEZEY, E SKIRBOLL, LR HOKFELT, T AF PALKOVITS, M MEZEY, E SKIRBOLL, LR HOKFELT, T TI ADRENERGIC PROJECTIONS FROM THE LOWER BRAIN-STEM TO THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS, THE LATERAL HYPOTHALAMIC AREA AND THE CENTRAL NUCLEUS OF THE AMYGDALA IN RATS SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article ID PHENYLETHANOLAMINE-N-METHYLTRANSFERASE; CORTICOTROPIN-RELEASING-FACTOR; CONTAINING CELL-BODIES; MEDULLA-OBLONGATA; VENTROLATERAL MEDULLA; IMMUNOHISTOCHEMICAL EVIDENCE; GLUCOCORTICOID RECEPTOR; SYNTHESIZING NEURONS; TYROSINE-HYDROXYLASE; SUPRAOPTIC NUCLEI AB Fine networks of phenylethanolamine N-methyltransferase (PNMT)-immunoreactive fibers are found in the hypothalamic paraventricular nucleus-mainly in the anterior, dorsal and dorso-medial parvicellular subdivisions, the lateral hypothalamus (dorsal, lateral and ventral to the fornix) and in the central amygdaloid nucleus. Coronal hemisections of the brainstem through the rostral level of the medulla oblongata show that most hypothalamic and amygdaloid PNMT fibers arise from the medullary adrenergic cell groups. Fourteen, but not 10 days after total hemisections, PNMT fibers disappeared almost completely from the hypothalamus and amygdala, ipsilateral to the knife cuts. A small decrease was also observed in the ventral, lateral hypothalamus on the contralateral side. Partial depletion of PNMT-immunoreactivity in the hypothalamus and the amygdala after medial or lateral brainstem hemisections indicates that ascending PNMT-immunoreactive fibers pass through mainly the lateral portion of the medulla, but some fibers also in its medial portion. Midsagittal transection of the diencephalon slightly reduced PNMT immunostaining in the paraventricular nucleus and the lateral hypothalamus bilaterally, The results show that the ascending PNMT system essentially is ipsilateral, but probably with a small crossing-over component, both at the diencephalic and lower brainstem level. C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. KAROLINSKA INST,DEPT HISTOL,S-10401 STOCKHOLM 60,SWEDEN. SEMMELWEIS UNIV MED,DEPT ANAT 1,H-1085 BUDAPEST 8,HUNGARY. RP PALKOVITS, M (reprint author), NIMH,CELL BIOL LAB,BLDG 36,RM 3A-17,BETHESDA,MD 20892, USA. RI Palkovits, Miklos/F-2707-2013 NR 54 TC 47 Z9 47 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD SEP-OCT PY 1992 VL 5 IS 5 BP 407 EP 415 DI 10.1016/0891-0618(92)90057-W PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JR782 UT WOS:A1992JR78200007 PM 1418754 ER PT J AU ZWANZIG, R AF ZWANZIG, R TI DYNAMIC DISORDER - PASSAGE THROUGH A FLUCTUATING BOTTLENECK SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article AB A model is proposed for a rate process that is controlled by passage through a fluctuating bottleneck. The rate of passage is proportional to the cross-sectional area of the bottleneck. The radius of the bottleneck fluctuates in time according to a Langevin equation with a decay constant lambda. Two consequences of the model are (1) decay is not exponential at short times, but changes to exponential at long times. (2) In the limit of small lambda, the resulting effective rate constant at long times is proportional to lambda-1/2. Predictions of the model are qualitatively consistent with experimental observations on the viscosity dependence of ligand motion in myoglobin. RP ZWANZIG, R (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. NR 5 TC 142 Z9 144 U1 3 U2 17 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD SEP 1 PY 1992 VL 97 IS 5 BP 3587 EP 3589 DI 10.1063/1.462993 PG 3 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA JL372 UT WOS:A1992JL37200078 ER PT J AU ZHOU, HX BAGCHI, B AF ZHOU, HX BAGCHI, B TI DIELECTRIC AND ORIENTATIONAL RELAXATION IN A BROWNIAN DIPOLAR LATTICE SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID COMPUTER-SIMULATION; MOLECULAR-REORIENTATION; POLAR LIQUIDS; FRICTION; CONSTANT AB In this article, both numerical and analytical studies of dielectric and orientational relaxation in a simple model system are presented. The system consists of point dipoles fixed at the sites of a simple cubic lattice. The dipoles are free to undergo rotational Brownian motion in the force field of all the other dipoles of the system. The dynamics in this simple model is described essentially by only one parameter eta = 1/3-rho-mu-2/k(B)T, where rho is the number density, mu is the dipole moment, and k(B)T is the Boltzmann constant times the temperature. Extensive Brownian dynamics simulations are carried out to obtain the frequency-dependent dielectric function of this system. The dielectric function becomes progressively non-Debye as the polarity of the system is increased. A comparison between single particle and collective moment-moment time correlation functions is made. It is found that at high polarities, the collective correlation function decays much faster than the single particle function, although a slowly decaying component develops for the collective function. The projection operator technique is used to derive a perturbative equation of motion for the dipole moment at any lattice site-the equation is exact to the second order in eta. This approach is quite successful in explaining the single particle dynamics. The perturbative equation also accounts for the progressively faster initial decay of the collective correlation function as eta increases. However, it fails to describe the slowly decaying component and consequently the observed non-Debye behavior at large eta. We also make a detailed comparison of the simulation results with the self-consistent continuum model of Nee and Zwanzig. It is found that the generalized diffusion equation is reliable if an accurate dielectric friction is used (from simulation, for example). However, the other ingredients of the continuum model are inadequate to describe the dielectric relaxation in this system. In particular, the predicted torque-torque correlation function decays too rapidly compared to the simulation results. RP ZHOU, HX (reprint author), NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Zhou, Huan-Xiang/M-5170-2016; OI Zhou, Huan-Xiang/0000-0001-9020-0302; BAGCHI, BIMAN/0000-0002-7146-5994 NR 30 TC 33 Z9 33 U1 0 U2 6 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD SEP 1 PY 1992 VL 97 IS 5 BP 3610 EP 3620 DI 10.1063/1.462944 PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA JL372 UT WOS:A1992JL37200081 ER PT J AU RANDOLPH, C GOLD, JM CARPENTER, CJ GOLDBERG, TE WEINBERGER, DR AF RANDOLPH, C GOLD, JM CARPENTER, CJ GOLDBERG, TE WEINBERGER, DR TI RELEASE FROM PROACTIVE-INTERFERENCE - DETERMINANTS OF PERFORMANCE AND NEUROPSYCHOLOGICAL CORRELATES SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID KORSAKOFFS SYNDROME; AMNESIC PATIENTS; HEAD-INJURY; MEMORY; SCHIZOPHRENIA; DYSFUNCTION; DEFICITS; IMPAIRMENT; CATEGORIES; DISEASE AB The Wickens (1970) modification of the Brown-Peterson short-term memory task has been used to investigate release from proactive interference (PI) in a number of memory-impaired groups. It has been suggested that failure to release from PI is observed only in patients with compromise of both memory and 'frontal-lobe' functions. The present study examined performance on this paradigm in patients with schizophrenia (SC), a neuropsychiatric disorder which typically includes both frontal and mnemonic impairments. Patients with SC were found to exhibit significantly less release from PI than normal controls. It was determined through correlational analyses that average Trial 1 performance on this task could predict performance on all subsequent trials, indicating that 'release' from PI may measure the same psychological process as the Brown-Peterson task, which does not include a release condition. Trial 1 performance in the SC group was correlated with a wide range of neuropsychological measures, but after the effect of full scale IQ was partialled out, only correlations with measures of memory and measures of frontal-lobe function remained significant. The results support previous formulations of the neuropsychological concomitants of release from PI, but suggest that failure to release on this paradigm may be secondary to a significant compromise of the ability to perform the Brown-Peterson task. It is proposed that the experimental design constraints necessary to elicit a failure to release from PI in any patient group may limit the utility of this measure, and that Brown-Peterson performance may be a more reliable index of the neuropsychological functions involved. C1 NIMH,IRP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 44 TC 25 Z9 25 U1 2 U2 4 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD SEP PY 1992 VL 14 IS 5 BP 785 EP 800 DI 10.1080/01688639208402863 PG 16 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA JY191 UT WOS:A1992JY19100011 PM 1474146 ER PT J AU COUNTS, DR GWIRTSMAN, H CARLSSON, LMS LESEM, M CUTLER, GB AF COUNTS, DR GWIRTSMAN, H CARLSSON, LMS LESEM, M CUTLER, GB TI THE EFFECT OF ANOREXIA-NERVOSA AND REFEEDING ON GROWTH HORMONE-BINDING PROTEIN, THE INSULIN-LIKE GROWTH-FACTORS (IGFS), AND THE IGF-BINDING PROTEINS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SOMATOMEDIN-C; FACTOR-I; SERUM; SECRETION; RECEPTOR; WEIGHT; VARIABLES; SITES; RATS; GH AB We studied the relationship of serum insulin-like growth factor-I (IGF-I), IGF-II, the IGF-binding proteins IGFBP-1, IGFBP-2, and IGFBP-3, and GH-binding protein (GHBP; which is postulated to be derived from the extracellular portion of the GH receptor) in normal volunteers and patients with anorexia nervosa before and after a refeeding program. Serum GHBP, IGF-I, and IGFBP-3 were all significantly decreased in low weight patients with anorexia nervosa and returned to nearly normal levels with refeeding. Fasting serum GH and serum IGFBP-1 and IGFBP-2 were significantly increased in low weight patients with anorexia nervosa and also returned to nearly normal levels with refeeding. Serum IGF-II was 27% lower in the low weight group than in normal subjects, but this difference was not statistically significant. Both serum IGF-I and IGF-II were positively correlated with serum IGFBP-3 and negatively correlated with serum IGFBP-1 and IGFBP-2. These data are consistent with the hypothesis that nutritional deprivation alters the GH-IGF axis by down-regulation of the GH receptor or its postreceptor mechanisms, and that this effect is reversible with refeeding. C1 NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. GENENTECH INC, ENDOCRINE RES DEPT, SAN FRANCISCO, CA 94080 USA. RP COUNTS, DR (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. OI Carlsson Ekander, Lena/0000-0003-4145-6242 NR 27 TC 271 Z9 273 U1 4 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1992 VL 75 IS 3 BP 762 EP 767 DI 10.1210/jc.75.3.762 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JM350 UT WOS:A1992JM35000015 PM 1381372 ER PT J AU SAJI, M MORIARTY, J BAN, T SINGER, DS KOHN, LD AF SAJI, M MORIARTY, J BAN, T SINGER, DS KOHN, LD TI MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENE-EXPRESSION IN RAT-THYROID CELLS IS REGULATED BY HORMONES, METHIMAZOLE, AND IODIDE AS WELL AS INTERFERON SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DEOXYRIBONUCLEIC-ACID SYNTHESIS; GROWTH FACTOR-I; THYROTROPIN RECEPTOR; ANTITHYROID DRUGS; GRAVES-DISEASE; FRTL-5 CELLS; THYROGLOBULIN; AUTOANTIBODIES; MECHANISM; ANTIGEN AB Autoimmune thyroid disease is associated with enhanced expression of major histocompatibility complex class I antigens on thyrocytes. To better understand this phenomenon, we have studied the normal expression of class I genes in FRTL-5 rat thyroid cells. A variety of hormones and growth factors that regulate the growth and function of these thyroid cells were found to decrease class I RNA levels: serum, insulin or insulin-like growth factor-I (IGF-I), and hydrocortisone. Antibody preparations from Graves' patients (thyroid-stimulating antibodies), which increase cAMP levels and stimulate the thyroid, also decrease class I RNA levels. This is consistent with the fact that TSH, via its cAMP signal, reduces class I transcripts. The class I response to TSH, serum, insulin, IGF-I, or hydrocortisone is specific, in that the same agents do not similarly affect TSH receptor, thyroglobulin, thyroid peroxidase, malic enzyme, or beta-actin RNA levels. Both gamma- and alpha-interferon increase class I RNA levels in FRTL-5 cells, even in the presence of the serum, IGF-I, or hormones noted above, i.e. they overcome hormonal negative regulation in normal thyrocytes. In contrast, methimazole treatment of rat FRTL-5 thyroid cells, but not rat fibroblasts or rat FRT thyroid cells, which have no TSH receptor and no TSH-regulated function, results in reduced class I RNA levels. The action of methimazole can inhibit interferon action, is transcriptional, is duplicated by iodide, and is additive with the negative regulatory action of hormones and serum factors, including TSH. C1 NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. NIH, BETHESDA, MD 20892 USA. RP SAJI, M (reprint author), NIDDKD, BIOCHEM & METAB LAB, BLDG 10, ROOM 9B13, BETHESDA, MD 20892 USA. RI Saji, Motoyasu/E-4007-2011 NR 36 TC 81 Z9 81 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1992 VL 75 IS 3 BP 871 EP 878 DI 10.1210/jc.75.3.871 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JM350 UT WOS:A1992JM35000034 PM 1381373 ER PT J AU CHIN, E BONDY, C AF CHIN, E BONDY, C TI INSULIN-LIKE GROWTH-FACTOR SYSTEM GENE-EXPRESSION IN THE HUMAN KIDNEY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; FACTOR-BINDING-PROTEINS; I IGF-I; RENAL HYPERTROPHY; CELLULAR-PATTERN; RECEPTOR; RATS; INCREASES; RNA AB Insulin-like growth factors (IGFs) have significant effects on renal function and have been implicated in renal development and hypertrophy. In order to investigate the renal IGF system in the human, we have used in situ hybridization to map the patterns of gene expression for IGF-I, IGF-II, IGF binding proteins-1 and -2 and both the type-I and type-II IGF receptors in the adult kidney. Since the rat is a model for the study of IGFs in renal physiology and pathophysiology, we compared patterns of IGF gene expression in the rat and human kidney. IGF-I messenger RNA (mRNA) is not detected in the human but is abundant in the rat kidney, while IGF-IL is abundant in the human but not detected in the adult rat kidney. IGF-II mRNA is concentrated in renal vascular system, including afferent arterioles and the medullary interstitium. IGF-I and IGF binding protein-1 mRNAs are colocalized in the rat medullary thick ascending limbs of Henle's loops, but neither is detected in the human kidney. IGF binding protein-2 mRNA is concentrated in glomeruli in both species, but, whereas in the human it is expressed in the epithelium of the distal nephron and collecting ducts, in the rat it is localized in the medullary interstitium. The patterns for both type-I and type-II IGF receptor gene expression are identical in both species; however, type-I receptor, mRNA is distinctly more abundant than type-II. Bath IGF receptor mRNAs are abundant in the renal tubular epithelium of the medulla and both are barely detectable in proximal tubules. Type I receptor mRNA alone is abundant in glomerular structures. These observations suggest that the autocrine/paracrine roles of IGFs are quite different in rat and human kidney. The conserved patterns of IGF receptor expression, however, suggests that the role of circulating IGFs in regulating renal function may be similar across the species. RP CHIN, E (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 35 TC 69 Z9 70 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1992 VL 75 IS 3 BP 962 EP 968 DI 10.1210/jc.75.3.962 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JM350 UT WOS:A1992JM35000050 PM 1381376 ER PT J AU FARRELL, WE CLARK, AJL STEWART, MF CROSBY, SR WHITE, A AF FARRELL, WE CLARK, AJL STEWART, MF CROSBY, SR WHITE, A TI BROMOCRIPTINE INHIBITS PROOPIOMELANOCORTIN MESSENGER-RNA AND ACTH PRECURSOR SECRETION IN SMALL-CELL LUNG-CANCER CELL-LINES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE BROMOCRIPTINE; PROOPIOMELANOCORTIN; ECTOPIC; SMALL CELL LUNG CANCER ID CUSHINGS-DISEASE; PEPTIDE SECRETION; INTERMEDIATE LOBE; GENE-EXPRESSION; PITUITARY; PROOPIOMELANOCORTIN; ADRENOCORTICOTROPIN; FRAGMENTS; CARCINOMA; ADENOMAS AB We have previously reported that a human small cell lung cancer (SCLC) cell line (COR L103) that expresses the proopiomelanocortin (POMC) gene and secretes ACTH precursor peptides is relatively resistant to glucocorticoid regulation. Using this model, we have now examined alternative regulatory mechanisms of the POMC gene and found that both the mRNA and ACTH precursor peptides were stimulated four- and two-fold, respectively, after 48 h incubation with db-cAMP. Next, we examined the dopamine agonist, bromocriptine, which acts predominantly through D2 receptors linked to adenyl cyclase to cause a reduction in intracellular cAMP. Bromocriptine suppressed cAMP levels and inhibited precursor peptide secretion within 24 h in a dose-dependent manner (0.15-15-mu-M). At the highest dose, peptide secretion was inhibited from 95 to 53 pmol/mg protein, and POMC mRNA was reduced by 50%, while, beta-actin mRNA remained unchanged. This effect could not be mimicked by incubation of cells with the alpha-adrenergic antagonist, phenoxybenzamine, suggesting that the alpha-adrenergic effects of bromocriptine were not responsible for this observation. These cells also secrete estradiol, but the secretory rate was unaffected by bromocriptine, suggesting, with the beta-actin data, that the POMC inhibition was not a cytotoxic effect. No recovery in precursor peptide secretion was seen in a 48-h period after the removal of bromocriptine. However, when the postchallenge incubation was extended to 8 d, there was a recovery in secretory potential between day 3 and day 8 and normal growth kinetics in the 4 d after removal of the drug. In contrast to these findings, the mouse corticotroph cell line, AtT20, showed no response to bromocriptine, in keeping with reports that this agonist has no effect on anterior lobe corticotrophs. We conclude that bromocriptine effectively inhibits POMC expression in SCLC cells, and that this phenomenon might be of useful clinical application. C1 UNIV MANCHESTER,HOPE HOSP,DEPT MED ECCLES OLD RD,SALFORD M6 8HD,LANCS,ENGLAND. MANCHESTER ROYAL INFIRM,DEPT CLIN PATHOL,MANCHESTER M13 9WL,LANCS,ENGLAND. NIH,ENDOCRINE & REPROD RES BRANCH,BETHESDA,MD 20892. RI White, Anne/C-3753-2011 NR 24 TC 16 Z9 16 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1992 VL 90 IS 3 BP 705 EP 710 DI 10.1172/JCI115941 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JN959 UT WOS:A1992JN95900004 PM 1325994 ER PT J AU FERRARO, R LILLIOJA, S FONTVIEILLE, AM RISING, R BOGARDUS, C RAVUSSIN, E AF FERRARO, R LILLIOJA, S FONTVIEILLE, AM RISING, R BOGARDUS, C RAVUSSIN, E TI LOWER SEDENTARY METABOLIC-RATE IN WOMEN COMPARED WITH MEN SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE 24-HOUR ENERGY EXPENDITURE; INDIRECT CALORIMETRY; SEX ID RESTING ENERGY-EXPENDITURE; MENSTRUAL-CYCLE; BODY-WEIGHT; CALORIMETER; HUMANS; GROWTH AB Since females have a greater prevalence of obesity compared with males, the question arises whether females have lower metabolic rate than males after adjusting for differences in body weight and composition. 24-h energy expenditure (24EE), basal metabolic rate (BMR), and sleeping metabolic rate (SMR) were measured in a respiratory chamber in 235 healthy, nondiabetic Caucasian subjects (114 males, 121 females). Body composition was determined by hydrodensitometry. 24EE was 124+/-38 kcal/d (P < 0.002) higher in males than females after adjusting for differences in fat-free mass, fat mass, and age. Spontaneous physical activity was not significantly different between males and females. Since adjusted 24EE was 106+/-39 kcal/d (P < 0.01) higher in females during the luteal phase of the menstrual cycle compared with females during the follicular phase, energy expenditure was analyzed in a subset (> 50 yr) to minimize the confounding effect of menstrual status. 24EE (160+/-66 kcal/d; P < 0.03), BMR (116+/-45; P < 0.02), and SMR (208+/-68 kcal/d; P < 0.005) were higher in males compared with females of the older subset after adjusting for differences in body composition, age, and activity. In summary, sedentary 24EE is approximately 5-10% lower in females compared with males after adjusting for differences in body composition, age, and activity. C1 NIDDK,CLIN DIABET & NUTR SECT,4212 N 16TH ST,ROOM 541,PHOENIX,AZ 85016. RI Lillioja, Stephen/A-8185-2012; OI Lillioja, Stephen/0000-0001-5333-5240 NR 32 TC 138 Z9 139 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1992 VL 90 IS 3 BP 780 EP 784 DI 10.1172/JCI115951 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JN959 UT WOS:A1992JN95900014 PM 1522233 ER PT J AU CHU, CS TRAPNELL, BC CURRISTIN, SM CUTTING, GR CRYSTAL, RG AF CHU, CS TRAPNELL, BC CURRISTIN, SM CUTTING, GR CRYSTAL, RG TI EXTENSIVE POSTTRANSCRIPTIONAL DELETION OF THE CODING SEQUENCES FOR PART OF NUCLEOTIDE-BINDING FOLD-1 IN RESPIRATORY EPITHELIAL MESSENGER-RNA TRANSCRIPTS OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE IS NOT ASSOCIATED WITH THE CLINICAL MANIFESTATIONS OF CYSTIC-FIBROSIS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE BRONCHIAL EPITHELIUM; EXON; SPLICING; POLYMERASE CHAIN REACTION ID DEPENDENT PROTEIN-KINASE; IDIOPATHIC PULMONARY FIBROSIS; CHLORIDE CHANNELS; R-DOMAIN; CFTR; CELLS; IDENTIFICATION; MUTATIONS; EXPRESSION; DNA AB Cystic fibrosis (CF) is a recessive hereditary disorder, requiring both parental cystic fibrosis conductance transmembrane regulator (CFTR) genes to carry mutations for clinical disease to manifest, i.e., only 50% of normal CFTR gene expression is required to maintain a normal phenotype. To help define the minimum amount of normal CFTR gene expression necessary to maintain normalcy, we have capitalized on our prior observation (Chu, C.-S, B. C. Trapnell, J. J. Murtagh, Jr., J. Moss, W. Dalemans, S. Jallat, A. Mercenier, A. Pavirani, J.-P. Lecocq, G. R. Cutting, et al. 1991. EMBO [Eur. Mol. Biol. Organ.] J. 10:1 355-1363) that normal individuals can have up to 66% of bronchial CFTR mRNA transcripts that are missing exon 9, a region representing 21% of the sequence coding for the critical nucleotide (ATP)-binding fold 1 (NBF1) of the predicted CFTR protein. The study population included 78 individuals with no prior diagnosis of CF. Evaluation of bronchial epithelial cells (obtained by bronchoscopy) revealed that exon 9 was variably deleted in all individuals. Remarkably, there were four individuals, all greater-than-or-equal-to 35 yr, in whom bronchial epithelial cells exhibited 73, 89, 90, and 92% CFTR transcripts with inframe deletion of exon 9, respectively, despite normal sweat Cl- and no clinical manifestation of CF. In the context that only 8% or less of bronchial CFTR transcripts need exon 9 to maintain normal airway function, these observations strongly suggest that either exon 9 is not necessary for CFTR structure and/or function or that only a very small fraction of bronchial epithelial cells need to express normal CFTR mRNA transcripts with exon 9 to perform the function of CFTR sufficient to maintain a normal phenotype in vivo. C1 JOHNS HOPKINS UNIV HOSP,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,CTR MED GENET,BALTIMORE,MD 21205. RP CHU, CS (reprint author), NHLBI,PULM BRANCH,BLDG 10,ROOM 6DO3,BETHESDA,MD 20892, USA. NR 40 TC 94 Z9 95 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1992 VL 90 IS 3 BP 785 EP 790 DI 10.1172/JCI115952 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JN959 UT WOS:A1992JN95900015 PM 1381723 ER PT J AU AMAGAI, M KARPATI, S PRUSSICK, R KLAUSKOVTUN, V STANLEY, JR AF AMAGAI, M KARPATI, S PRUSSICK, R KLAUSKOVTUN, V STANLEY, JR TI AUTOANTIBODIES AGAINST THE AMINO-TERMINAL CADHERIN-LIKE BINDING DOMAIN OF PEMPHIGUS-VULGARIS ANTIGEN ARE PATHOGENIC SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ACANTHOLYSIS; AUTOIMMUNITY; CELL ADHESION; DESMOSOME; IMMUNOGENIC DOMAIN ID CELL-ADHESION MOLECULES; DESMOSOMAL GLYCOPROTEIN; PLACENTAL CADHERIN; SEQUENCE-ANALYSIS; GENE FAMILY; FOLIACEUS; IDENTIFICATION; CDNA; EXPRESSION; DESMOGLEIN AB Complementary DNA cloning of the 130-kD pemphigus vulgaris (PV) autoantigen (PVA) has indicated that it is a member of the cadherin family of Ca2+-dependent cell adhesion molecules. By homology with typical cadherins, PVA has five extracellular domains (EC1 through EC5). To localize immunogenic domains and to determine whether antibodies against them might be pathogenic, we produced beta-galactosidase fusion proteins with cDNA encoding different portions of the extracellular domains of PVA (EC1-2, EC3-5, and each individual domain). Immunoblot analysis of these fusion proteins with 23 PV patients' sera demonstrated that major immunogenic regions of PVA are located on the EC1, EC2, and EC4 domains. IgG was affinity-purified from PV sera on fusion proteins representing the amino (EC1-2) and carboxy (EC3-5) terminus of the extracellular PVA, and injected into neonatal mice. PV IgG affinity-purified on the EC1-2 fusion protein caused suprabasilar acantholysis, the typical histological finding of PV, but IgG affinity-purified on the EC3-5 fusion protein or beta-galactosidase alone did not. These results indicate that at least one pathogenic epitope, which is sufficient to cause suprabasilar acantholysis in neonatal mice, is located on the amino-terminal region of PVA, an area thought to be important in cadherin homophilic adhesion. RP AMAGAI, M (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,BETHESDA,MD 20892, USA. RI Amagai, Masayuki/K-5325-2013 OI Amagai, Masayuki/0000-0003-3314-7052 NR 35 TC 252 Z9 255 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1992 VL 90 IS 3 BP 919 EP 926 DI 10.1172/JCI115968 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JN959 UT WOS:A1992JN95900031 PM 1522242 ER PT J AU TAKAGI, H JHAPPAN, C SHARP, R MERLINO, G AF TAKAGI, H JHAPPAN, C SHARP, R MERLINO, G TI HYPERTROPHIC GASTROPATHY RESEMBLING MENETRIERS DISEASE IN TRANSGENIC MICE OVEREXPRESSING TRANSFORMING GROWTH FACTOR-ALPHA IN THE STOMACH SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE MENETRIERS DISEASE; TRANSFORMING GROWTH FACTOR-ALPHA; TRANSGENIC MICE; STOMACH; PARIETAL CELLS ID TGF-ALPHA; RAT FIBROBLASTS; FACTOR RECEPTOR; CELLS; EXPRESSION; HYPERPLASIA; SECRETION; NEOPLASIA; PANCREAS; GLAND AB Transforming growth factor-alpha (TGF-alpha) is thought to participate in the normal and pathologic processes of numerous tissues, including the gastric mucosa. To explore its role in vivo, transgenic mice were generated overexpressing TGF-alpha in the stomach. TGF-alpha induced dramatic structural and functional lesions of the glandular stomach that were similar to Menetrier's disease in humans. Transgenic mice developed severe adenomatous hyperplasia that resulted in a striking nodular thickening or hypertrophy of the gastric mucosa. Secretions obtained from affected stomachs contained no detectable gastric acid, suggesting that parietal cell function had been greatly impaired. These findings demonstrate that overproduction of TGF-alpha can stimulate cellular proliferation, suppress acid secretion, and perturb organogenesis of the stomach of transgenic mice. Moreover, TGF-alpha may contribute to the pathogenesis of related human hypertrophic gastropathies, such as Menetrier's disease. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 29 TC 118 Z9 120 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1992 VL 90 IS 3 BP 1161 EP 1167 DI 10.1172/JCI115936 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JN959 UT WOS:A1992JN95900064 PM 1522224 ER PT J AU RUBENSTEIN, CS PIGOTT, TA LHEUREUX, F HILL, JL MURPHY, DL AF RUBENSTEIN, CS PIGOTT, TA LHEUREUX, F HILL, JL MURPHY, DL TI A PRELIMINARY INVESTIGATION OF THE LIFETIME PREVALENCE OF ANOREXIA AND BULIMIA-NERVOSA IN PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID EATING DISORDERS; COMORBIDITY; SEROTONIN AB Background: Obsessive compulsive disorder (OCD) is currently classified as an anxiety disorder although it possesses many characteristics that distinguish it from other anxiety disorders. Clinically and neurobiologically, OCD appears to overlap somewhat with the eating disorders. Method: To assess in a controlled fashion the lifetime prevalence of the eating disorders in patients with OCD, we administered portions of the Structured Clinical Interview for DSM-III-R, Patient Version (SCID-P), to 62 patients (31 men, 31 women) with a primary DSM-III-R diagnosis of OCD. Results: Among the OCD patients, the lifetime prevalence of anorexia nervosa and/or bulimia nervosa was 12.9 % (N = 8), and an additional 17.7 % (N = 11) met subthreshold criteria for either anorexia or bulimia nervosa. Interestingly, unlike multiple epidemiologic studies that have r e ported a substantial female preponderance among patients diagnosed with anorexia or bulimia nervosa, there was no significant gender difference in the lifetime prevalence of eating disorders among the patients with OCD. Almost 13% (N = 4) of the men and 6.5% (N = 2) of the women with OCD met criteria for a lifetime diagnosis of anorexia nervosa and 3.2 % (N = 1) of the men and 6.5% (N = 2) of the women with OCD met criteria at some time in their lives for bulimia nervosa. In addition, subthreshold criteria for anorexia nervosa or bulimia nervosa were met by an additional 12.9% (N = 4) of the men and 22.6 % (N = 7) of the women. Conclusion: These data suggest that OCD patients, regardless of gender, have a substantial lifetime prevalence of anorexia and/or bulimia nervosa. C1 NIMH, CTR CLIN,CLIN SCI LAB,CLIN NEUROPHARMACOL SECT, 10-3D41,9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 40 TC 64 Z9 65 U1 1 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 1992 VL 53 IS 9 BP 309 EP 314 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA JN801 UT WOS:A1992JN80100002 PM 1517192 ER PT J AU HORWITZ, B GRADY, CL HAXBY, JV SCHAPIRO, MB RAPOPORT, SI UNGERLEIDER, LG MISHKIN, M AF HORWITZ, B GRADY, CL HAXBY, JV SCHAPIRO, MB RAPOPORT, SI UNGERLEIDER, LG MISHKIN, M TI FUNCTIONAL ASSOCIATIONS AMONG HUMAN POSTERIOR EXTRASTRIATE BRAIN-REGIONS DURING OBJECT AND SPATIAL VISION SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID CEREBRAL METABOLIC RATES; GLUCOSE-UTILIZATION; MENTAL ROTATION; LEFT-HEMISPHERE; BLOOD-FLOW; INTERCORRELATIONS; RECOGNITION; LESIONS; PATTERN; CORTEX AB Primate extrastriate visual cortex is organized into an occipitotemporal pathway for object vision and an occipitoparietal pathway for spatial vision. Correlations between normalized regional cerebral blood flow values (regional divided by global flows), obtained using (H2O)-O-15 and positron emission tomography, were used to examine functional associations among posterior brain regions for these two pathways in 17 young men during performance of a face matching task and a dot-location matching task. During face matching, there was a significant correlation in the right hemisphere between an extrastriate occipital region that was equally activated during both the face matching and dot-location matching tasks and a region in inferior occipitotemporal cortex that was activated more during the face matching task. The corresponding correlation in the left hemisphere was not significantly different from zero. Significant intrahemispheric correlations among posterior regions were observed more often for the right than for the left hemisphere. During dot-location matching, many significant correlations were found among posterior regions in both hemispheres, but significant correlations between specific regions in occipital and parietal cortex shown to be reliably activated during this spatial vision test were found only in the right cerebral hemisphere. These results suggest that (1) correlational analysis of normalized rCBF can detect functional interactions between components of proposed brain circuits, and (2) face and dot-location matching depend primarily on functional interactions between posterior cortical areas in the right cerebral hemisphere. At the same time, left hemisphere cerebral processing may contribute more to dot-location matching than to face matching. C1 NIMH,BETHESDA,MD 20892. RP HORWITZ, B (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C-414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 56 TC 109 Z9 109 U1 1 U2 6 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD ST JOURNALS DEPT, CAMBRIDGE, MA 02142 SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD FAL PY 1992 VL 4 IS 4 BP 311 EP 322 DI 10.1162/jocn.1992.4.4.311 PG 12 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA JU789 UT WOS:A1992JU78900002 PM 23968125 ER PT J AU STERNBERG, KJ LAMB, ME AF STERNBERG, KJ LAMB, ME TI EVALUATIONS OF ATTACHMENT RELATIONSHIPS BY JEWISH ISRAELI DAY-CARE PROVIDERS SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article ID STRANGE SITUATION AB Israeli day-care providers (N = 109) viewed one 20-minute videotape of a mother and infant interacting in the Strange Situation. After viewing the videotape, subjects completed a questionnaire that included items related to the labeling and evaluation of infant behavior in the Strange Situation. In addition, subjects were asked to rank order eight definitions-descriptions of the eight subcategories comprising the traditional categorical system on how well they described the infant in the videotape. On 12 of the 16 labeling and evaluation items, groups were significantly differentiated, with most differences in the expected direction. Sixty-one percent of the care providers ranked the correct classification as their first or second choice, and 82% of the care providers who did not rank the correct definition in first or second place classified the infant in a conceptually adjacent category. These Israeli Care providers preferred to interact with B2 infants and liked the C1 infants least, suggesting approval of independence on the part of young infants. The results of this study suggest that naive Israelis classify, label, and evaluate infants in a manner consistent with the explicit values of attachment theorists. RP STERNBERG, KJ (reprint author), NICHHD,SOCIAL & EMOTIONAL DEV SECT,BSA BLDG,ROOM 331,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 13 TC 1 Z9 1 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD SEP PY 1992 VL 23 IS 3 BP 285 EP 299 DI 10.1177/0022022192233001 PG 15 WC Psychology, Social SC Psychology GA JK531 UT WOS:A1992JK53100001 ER PT J AU NAKAGAWA, M LAMB, ME MIYAKI, K AF NAKAGAWA, M LAMB, ME MIYAKI, K TI ANTECEDENTS AND CORRELATES OF THE STRANGE SITUATION BEHAVIOR OF JAPANESE INFANTS SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article ID ATTACHMENT; RESPONSES; SECURITY; MOTHER AB Varying distributions across attachment classifications in different cultures have raised questions about the cross-cultural validity of the Strange Situation. These questions can be addressed by examining the antecedents and correlates of Strange Situation behavior outside the United States. If the Strange Situation is a mild-to-moderate stressor for both U.S. and Japanese infants, the antecedents and correlates of attachment classifications should be similar in both cultures. The present study examined the validity of the Strange Situation with Japanese infants and mothers by investigating the correlates and antecedents of Strange Situation behavior. In the United States, Ainsworth et al. reported that mothers' responsiveness to their infants was the best predictor of infants' later attachment classifications. Dickstein et al. found that resistant infants referenced their mothers most frequently, avoidant infants the least, and secure infants an intermediate amount. These findings suggested two hypotheses: Japanese infants should, like U.S. infants, reference their mothers differentially depending on their attachment classifications and "responsive" Japanese mothers should have "secure" infants. However, none of the statistical tests related to these hypotheses were significant. "Secure" and "resistant" Japanese infants were equally likely to reference their mothers, and maternal responsiveness was not associated with the infants' later attachment classifications. These results suggest that the Strange Situation may not be a valid index of the security of infant-mother attachment in Japan. C1 UNIV MARYLAND,DEPT PSYCHOL,COLL PK,MD 20742. HOKKAIDO UNIV,FAC EDUC,SAPPORO,HOKKAIDO 060,JAPAN. RP NAKAGAWA, M (reprint author), NICHHD,SOCIAL & EMOTIONAL DEV SECT,9190 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 21 TC 20 Z9 20 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD SEP PY 1992 VL 23 IS 3 BP 300 EP 310 DI 10.1177/0022022192233002 PG 11 WC Psychology, Social SC Psychology GA JK531 UT WOS:A1992JK53100002 ER PT J AU SAMUDZI, CT FIVASH, MJ ROSENBERG, JM AF SAMUDZI, CT FIVASH, MJ ROSENBERG, JM TI CLUSTER-ANALYSIS OF THE BIOLOGICAL MACROMOLECULE CRYSTALLIZATION DATABASE SO JOURNAL OF CRYSTAL GROWTH LA English DT Article ID PROTEIN CRYSTALLIZATION; GROWTH; CRYSTALS AB Cluster analysis was performed on the Biological Macromolecule Crystallization Database (BMCD) [1] in an effort to uncover trends useful in the crystallization of new macromolecules. The following crystallization parameters were used in defining an experiment; pH, temperature, molecular weight, macromolecular concentration, precipitant type and crystallization method. Using these parameters, a measure of the difference between experiments is developed. Groups or clusters of similar experiments are identified as those close together based upon the difference measure. Descriptive statistics were performed on each cluster. Since each cluster represents a well defined class of macromolecules, it seems reasonable to use the boundaries of conditions within each cluster as initial conditions when attempting to crystallize a new macromolecule. C1 UNIV PITTSBURGH,DEPT BIOL SCI,PITTSBURGH,PA 15260. RP SAMUDZI, CT (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 13 TC 21 Z9 22 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-0248 J9 J CRYST GROWTH JI J. Cryst. Growth PD SEP PY 1992 VL 123 IS 1-2 BP 47 EP 58 DI 10.1016/0022-0248(92)90009-8 PG 12 WC Crystallography; Materials Science, Multidisciplinary; Physics, Applied SC Crystallography; Materials Science; Physics GA JP483 UT WOS:A1992JP48300006 ER PT J AU KAUFMAN, E CHASTAIN, DC GAUGHAN, AM GRACELY, RH AF KAUFMAN, E CHASTAIN, DC GAUGHAN, AM GRACELY, RH TI STAIRCASE ASSESSMENT OF THE MAGNITUDE AND TIME-COURSE OF 50-PERCENT NITROUS-OXIDE ANALGESIA SO JOURNAL OF DENTAL RESEARCH LA English DT Article ID GENERAL-ANESTHETICS; PAIN; NALOXONE; REVERSAL; SUPPRESSION AB The analgesic effect of 50% nitrous oxide and oxygen on thermal pain sensations was evaluated in a placebo-controlled, double-blind crossover design. In a session immediately before oral surgery, 20 patients used a seven-point verbal scale to rate the intensity of pain sensations evoked by three-second thermal stimuli delivered to 14 sites on the volar forearm at 20-second intervals by a 1-cm-diameter contact thermode. Subjects rated 36 stimuli while breathing room air and then two additional sets of 36 stimuli while inhaling 50% nitrous oxide and oxygen during one set and oxygen placebo during the other. Each of these two stimulus sets was preceded by a two-minute induction of the agent, and the sets were separated by a three-minute washout period. Order of administration was randomized and counterbalanced. Stimulus temperatures were adjusted continuously by an interactive computer program so that response could be maintained at predetermined levels. This method resulted in a continuous measure of analgesia in units of stimulus intensity. Results showed that, in comparison with placebo, nitrous oxide significantly increased the stimulus temperatures (mean = 0.42-degrees-C) required to make the same response [F (11,209) = 6.76, p <0.0001], indicating analgesia. This increase was one-third to one-half that observed with clinical doses of intravenous fentanyl. Analgesic effects were apparent at three min and waned 10 min after termination of nitrous-oxide inhalation. These times closely correlated with previous measures of alveolar concentration, further supporting the fast but modest analgesic action of nitrous oxide. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,101N-103D,BETHESDA,MD 20892. NR 37 TC 6 Z9 6 U1 1 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 1992 VL 71 IS 9 BP 1598 EP 1603 DI 10.1177/00220345920710091001 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JP661 UT WOS:A1992JP66100010 PM 1522292 ER PT J AU BISWAS, P POLI, G KINTER, AL JUSTEMENT, JS STANLEY, SK MAURY, WJ BRESSLER, P ORENSTEIN, JM FAUCI, AS AF BISWAS, P POLI, G KINTER, AL JUSTEMENT, JS STANLEY, SK MAURY, WJ BRESSLER, P ORENSTEIN, JM FAUCI, AS TI INTERFERON-GAMMA INDUCES THE EXPRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS IN PERSISTENTLY INFECTED PROMONOCYTIC CELLS (U1) AND REDIRECTS THE PRODUCTION OF VIRIONS TO INTRACYTOPLASMIC VACUOLES IN PHORBOL-MYRISTATE ACETATE DIFFERENTIATED U1 CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; FACTOR-ALPHA; MONONUCLEAR PHAGOCYTES; U937 CELLS; PERIPHERAL-BLOOD; BONE-MARROW; HTLV-III; HIV; INVITRO AB Interferon-gamma (IFN-gamma), a lymphokine that exerts multiple immunoregulatory effects, has been found to be elevated in the plasma, cerebrospinal fluid, and lymph nodes of human immunodeficiency virus (HIV)-infected individuals and has shown variable effects on HIV replication in acutely infected cells. In the present study, we have demonstrated that IFN-gamma is a potent modulator of HIV expression in persistently infected U1 promonocytic cells in which virus production is characterized by a constitutive state of relative latency. Direct stimulation of U1 cells with IFN-gamma (10-1,000 U/ml) activated HIV expression, as measured by reverse transcriptase (RT) activity in the culture supernatant and increased levels of cell-associated viral protein and mRNAs. These effects on virus expression were not accounted for by the induction of endogenous TNF-alpha secretion, as previously described in U1 cells stimulated with phorbol myristate acetate (PMA). At the ultrastructural level, the stimulatory activity of IFN-gamma was correlated with HIV particle production in intracytoplasmic vacuoles along with the differentiation of U1 into macrophage-like cells. Furthermore, costimulation of U1 cells with IFN-gamma and PMA significantly increased the accumulation of vacuole-associated HIV concomitant with decreasing membrane-associated particles and RT activity production, as compared with cells stimulated with PMA alone. No evidence of spontaneous secretion of intracellular vacuole-associated virus was obtained by kinetic analysis of the RT activity released in the supernatants throughout the culture period unless cells were deliberately disrupted. These findings suggest that vacuole-associated virions likely represent a relatively stable intracellular reservoir of HIV, as previously described in primary macrophages infected in vitro or in infected macrophages in the brains of patients with acquired immune deficiency syndrome. The reduced levels of RT activity observed in the culture supernatants of U1 cells stimulated with PMA in the presence of IFN-gamma were not indicative of a suppressive effect of IFN-gamma on PMA-induced expression of HIV proteins and mRNAs, either directly or mediated by the release of IFN-alpha/beta. This study suggests that IFN-gamma may play an important role as an inducer of HIV expression in infected mononuclear phagocytes. C1 NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892. ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. NR 59 TC 148 Z9 148 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1992 VL 176 IS 3 BP 739 EP 750 DI 10.1084/jem.176.3.739 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JK427 UT WOS:A1992JK42700012 PM 1512539 ER PT J AU SADZIENE, A ROSA, PA THOMPSON, PA HOGAN, DM BARBOUR, AG AF SADZIENE, A ROSA, PA THOMPSON, PA HOGAN, DM BARBOUR, AG TI ANTIBODY-RESISTANT MUTANTS OF BORRELIA-BURGDORFERI - INVITRO SELECTION AND CHARACTERIZATION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LYME-DISEASE SPIROCHETE; VARIABLE MAJOR PROTEINS; MONOCLONAL-ANTIBODY; SURFACE PROTEIN; PASSIVE-IMMUNIZATION; NEUTRALIZATION SITE; ANTIGENIC VARIANTS; INFLUENZA-VIRUS; LSH HAMSTERS; GLYCOPROTEIN AB We used polyclonal antisera and monoclonal antibodies (mAbs) to inhibit the growth of clonal populations of two strains of Borrelia burgdorferi, the Lyme disease agent, and thereby select for antibody-resistant mutants. mAbs were directed at the outer membrane proteins, OspA or OspB. Mutants resistant to the growth-inhibiting properties of the antibodies were present in the populations at frequencies ranging from 10(-5) to 10(-2). The several escape variants that were examined were of four classes. Class I mutants were resistant to all mAbs; they lacked OspA and OspB and the linear plasmid that encodes them. Two other proteins were expressed in larger amounts in class I mutants; mAbs to these proteins inhibited the mutant but not the wild-type cells. Class II mutants were resistant to some but not all mAbs; they had truncated OspA and/or OspB proteins. Class III mutants were resistant only to the selecting mAb; they had full-length Osp proteins that were not bound by the selecting antibody in Western blots. In two class III mutants resistant to different anti-OspA mAbs, missense mutations were demonstrated in the ospA genes. Class IV mutants were likewise resistant only to selecting antibody, but in this case the selecting antibody still bound in Western blots. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MICROBIOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,BETHESDA,MD 20892. VILNIUS EXPTL & CLIN MED INST,VILNIUS 232000,LITHUANIA,USSR. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. RI Barbour, Alan/B-3160-2009 OI Barbour, Alan/0000-0002-0719-5248 FU NIAID NIH HHS [AI-29731] NR 59 TC 136 Z9 136 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1992 VL 176 IS 3 BP 799 EP 809 DI 10.1084/jem.176.3.799 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JK427 UT WOS:A1992JK42700018 PM 1339462 ER PT J AU VOLAREVIC, S NIKLINSKA, BB BURNS, CM YAMADA, H JUNE, CH DUMONT, FJ ASHWELL, JD AF VOLAREVIC, S NIKLINSKA, BB BURNS, CM YAMADA, H JUNE, CH DUMONT, FJ ASHWELL, JD TI THE CD45 TYROSINE PHOSPHATASE REGULATES PHOSPHOTYROSINE HOMEOSTASIS AND ITS LOSS REVEALS A NOVEL PATTERN OF LATE T-CELL RECEPTOR INDUCED CA2+ OSCILLATIONS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LEUKOCYTE-COMMON ANTIGEN; MONOCLONAL-ANTIBODY; DIFFERENTIATION ANTIGENS; INTERLEUKIN-2 PRODUCTION; PROTEIN-KINASE; FREE CALCIUM; ZETA-CHAIN; ACTIVATION; PHOSPHORYLATION; PP60C-SRC AB CD45 is a transmembrane tyrosine phosphatase implicated in T cell antigen receptor (TCR)-mediated activation. In T cell variants expressing progressively lower levels of CD45 (from normal to undetectable), CD45 expression was inversely related to spontaneous tyrosine phosphorylation of multiple proteins, including the TCR zeta-chain, and was directly correlated with TCR-driven phosphoinositide hydrolysis. The Ca2+ response in these cells was altered in an unexpected fashion. Unlike wild-type cells, stimulated CD45- cell populations did not manifest an early increase in intracellular Ca2+, but did exhibit a delayed and gradual increase in mean intracellular Ca2+. Computer-aided fluorescence imaging of individual cells revealed that CD45- cells experienced late Ca2+ oscillations that were not blocked by removal of extracellular Ca2+. CD45 revertants had the signaling properties of wild-type cells. Thus, CD45 has a profound influence on both TCR-mediated signaling and phosphotyrosine homeostasis, and its loss reveals a novel role for this tyrosine phosphatase in Ca2+ regulation. C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,IMMUNE CELL BIOL LAB,BLDG 10,BETHESDA,MD 20892. MERCK SHARP & DOHME LTD,DEPT IMMUNOL RES,RAHWAY,NJ 07065. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. NR 44 TC 90 Z9 90 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1992 VL 176 IS 3 BP 835 EP 844 DI 10.1084/jem.176.3.835 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JK427 UT WOS:A1992JK42700022 PM 1380977 ER PT J AU SNODGRASS, DR HOSHINO, Y FITZGERALD, TA SMITH, M BROWNING, GF GORZIGLIA, M AF SNODGRASS, DR HOSHINO, Y FITZGERALD, TA SMITH, M BROWNING, GF GORZIGLIA, M TI IDENTIFICATION OF 4 VP4 SEROLOGICAL TYPES (P-SEROTYPES) OF BOVINE ROTAVIRUS USING VIRAL REASSORTANTS SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; CALF DIARRHEA; GENOMIC CHARACTERIZATION; NEUTRALIZATION EPITOPES; NUCLEIC-ACID; YOUNG CALVES; UNIQUE VP4; INFECTION; VACCINE; STRAINS AB A series of five reassortant viruses each containing the VP4 gene of a distinct bovine rotavirus and the VP7 gene of human rotavirus strain ST3 was prepared, and antisera to these were produced in rabbits. In neutralization tests, these antisera allowed the differentiation of the five original strains (from three different VP7 or G serotypes) into three or possibly four VP4 or P serotypes. All of a further seven bovine rotavirus strains adapted to cell culture were successfully typed by these antisera. There was a degree of cross-reaction between antiserum to the fourth bovine rotavirus P serotype and the predominant human rotavirus serotype. However, antisera raised in guinea-pigs to recombinant VP4 from this serotype showed the bovine serotype to be distinct. There was no significant serological relationship between these four bovine rotavirus P serotypes and previously described P serotypes from rotaviruses isolated from man and non-bovine animals. The predominant bovine rotavirus VP7 serotypes G6 and G10 tended to have distinct P serotypes also. C1 NIH,INFECT DIS LAB,BETHESDA,MD 20892. RP SNODGRASS, DR (reprint author), MOREDUN RES INST,408 GILMERTON RD,EDINBURGH EH17 7JH,MIDLOTHIAN,SCOTLAND. NR 47 TC 44 Z9 45 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD SEP PY 1992 VL 73 BP 2319 EP 2325 DI 10.1099/0022-1317-73-9-2319 PN 9 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA JM525 UT WOS:A1992JM52500019 PM 1328488 ER PT J AU HOU, WY PIMENTA, PFP RULONG, S DASILVA, PP AF HOU, WY PIMENTA, PFP RULONG, S DASILVA, PP TI STEREO VIEWS AND IMMUNOGOLD LABELING OF THE PELLICULAR MICROTUBULES AT THE INNER SURFACE OF THE PLASMA-MEMBRANE OF LEISHMANIA AS REVEALED BY FRACTURE-FLIP SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE INNER SURFACE; FRACTURE-FLIP; LEISHMANIA MAJOR; MICROTUBULES; IMMUNOGOLD LABELING; TUBULIN; FREEZE-FRACTURE ID QUICK-FREEZE; PROMASTIGOTES AB We used a modification of fracture-flip to reveal the nanoanatomy of the inner surface of the plasma membrane in promastigotes of Leishmania. After freeze-fracture, lightly fixed promastigotes were coated with a stabilizing layer of carbon evaporated from an electron gun, thawed, and washed. Fractured promastigotes attached to the carbon casts by the protoplasmic (i.e., inner) halves of their plasma membranes were treated with Triton X-100, followed by exposure to low concentrations of trypsin and thorough washing. This was followed by picking up and flipping of the replicas, followed by air-drying. The actual inner surfaces of the plasma membrane were then imaged by platinum shadowing. Extended, three-dimensional, high-resolution views of the inner surface of the plasma membrane showed parallel arrays of microtubules (average spacing 47 nm) closely apposed to the inner surface. Cytochemical labeling confirmed the morphological identification of both subpellicular and flagellar microtubules, as determined by treatment with mouse monoclonal anti-alpha- or anti-beta-tubulin, followed by labeling with goat anti-mouse IgG adsorbed to colloidal gold. Removal of the microtubules revealed parallel arrays of particles (average diameter 17 nm). We hypothesize that these particles represent the cytoplasmic portion of proteins that link the microtubules to the plasma membrane. C1 NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,STRUCT BIOL SECT,FREDERICK,MD 21702. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NR 21 TC 6 Z9 6 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD SEP PY 1992 VL 40 IS 9 BP 1309 EP 1318 PG 10 WC Cell Biology SC Cell Biology GA JJ672 UT WOS:A1992JJ67200008 PM 1506668 ER PT J AU METZGER, H AF METZGER, H TI TRANSMEMBRANE SIGNALING - THE JOY OF AGGREGATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; EPIDERMAL GROWTH-FACTOR; HIGH-AFFINITY RECEPTOR; PROTEIN KINASE P56LCK; T-CELL; IMMUNOGLOBULIN-E; LATERAL DIFFUSION; IGE RECEPTORS; TYROSINE PHOSPHORYLATION; MEDIATED HYDROLYSIS RP NIAMS, RM 9N228, BLDG 10, BETHESDA, MD 20892 USA. NR 99 TC 213 Z9 215 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1992 VL 149 IS 5 BP 1477 EP 1487 PG 11 WC Immunology SC Immunology GA JJ890 UT WOS:A1992JJ89000001 PM 1324276 ER PT J AU HARA, Y CASPI, RR WIGGERT, B DORF, M STREILEIN, JW AF HARA, Y CASPI, RR WIGGERT, B DORF, M STREILEIN, JW TI ANALYSIS OF AN INVITRO-GENERATED SIGNAL THAT INDUCES SYSTEMIC IMMUNE DEVIATION SIMILAR TO THAT ELICITED BY ANTIGEN INJECTED INTO THE ANTERIOR-CHAMBER OF THE EYE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RESPONSES; MACROPHAGE HYBRIDOMAS; FUNCTIONAL-ANALYSIS; SOLUBLE-ANTIGEN; INDUCTION; ACAID; MICE; PROTEIN; TUMORS; BLOOD AB The selective deficit in delayed hypersensitivity that characterizes anterior chamber-associated immune deviation (ACAID) is the direct result of a blood borne, Ag-specific, cell-associated signal that is created after Ag is injected into the anterior chamber of the eye of normal mice. The cells that carry this signal via the blood to the spleen express the mature macrophage marker F4/80 and are similar to, or perhaps even arise from, F4/80+ dendritic cells found within the stroma of normal iris and ciliary body. We have recently reported that ACAID-inducing properties can be conferred upon conventional F4/80-bearing macrophages harvested from the normal peritoneal cavity by incubating these cells in vitro with the soluble protein Ag, BSA, in the presence of supernatants harvested from cultured iris and ciliary body cells. Using this in vitro induction system, we have examined the limiting conditions for conferring ACAID-inducing potential on peritoneal exudate cells. We have found that an ACAID-inducing signal can be created in vitro with several different soluble Ag, including the retinal autoantigen-interphotoreceptor retinol binding protein, and that active endocytosis and processing by peritoneal exudate cells is required because chloroquine prevents these cells from acquiring ACAID-inducing properties. In addition, we have determined that for supernatant-treated peritoneal macrophages to induce ACAID to soluble Ag the cells must be 1) alive, 2) injected i.v. or i.p. (but not s.c.), and 3) administered to recipients with an anatomically intact spleen. When these conditions are met, as few as 20 F4/80+ macrophages pulsed with Ag in the presence of iris and ciliary body supernatants are sufficient to induce ACAID. Macrophage hybridomas derived from 'conventional" APC can acquire ACAID-inducing potential in vitro if exposed to iris and ciliary body supernatants, whereas macrophage hybridomas derived from "suppressor inducer" APC constitutively possess ACAID-induced potential. Peritoneal macrophages that were endowed with ACAID-inducing properties by in vitro exposure to supernatants were found to elicit splenic suppressor cells similar to those found in spleens of mice with ACAID. Moreover, the expression of experimental autoimmune uveitis in mice immunized with interphotoreceptor retinol binding protein was significantly suppressed if the animals were pretreated with peritoneal exudate cells pulsed with this Ag in the presence of iris and ciliary body supernatants. These results extend our knowledge of the process by which ACAID is induced by revealing that antigen processing and presenting functions of viable F4/80+ macrophages are essential, that the cells carrying the ACAID signal must have direct access to the spleen, and that when these cells reach the spleen they evoke Ag-specific regulation that interferes with expression of delayed hypersensitivity and ocular autoimmunity. C1 UNIV MIAMI,SCH MED,DEPT MICROBIOL & IMMUNOL R138,POB 016960,MIAMI,FL 33101. UNIV MIAMI,SCH MED,DEPT OPHTHALMOL,MIAMI,FL 33101. NEI,IMMUNOL LAB,BETHESDA,MD 20892. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NEI NIH HHS [EY 05678] NR 26 TC 70 Z9 73 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1992 VL 149 IS 5 BP 1531 EP 1538 PG 8 WC Immunology SC Immunology GA JJ890 UT WOS:A1992JJ89000008 PM 1387141 ER PT J AU HIRUMA, K GRESS, RE AF HIRUMA, K GRESS, RE TI CYCLOSPORINE-A AND PERIPHERAL TOLERANCE - INHIBITION OF VETO CELL-MEDIATED CLONAL DELETION OF POSTTHYMIC PRECURSOR CYTOTOXIC LYMPHOCYTES-T SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VERSUS-HOST DISEASE; CLASS-I MHC; MESSENGER-RNA; BONE-MARROW; ANTIGEN RECEPTOR; TRANSGENIC MICE; ACTIVATION; RESPONSES; EXPRESSION; INVITRO AB Veto cell-mediated suppression of CTL responses has been proposed as one mechanism by which self tolerance is maintained in mature T cell populations. We have reported that murine bone marrow cells cultured in the presence of high-dose IL-2 (activated bone marrow cells) mediate strong veto suppressor function in vitro and in vivo, and that such veto activity is effected through clonal deletion of cytotoxic T cell precursors. In our studies, we have determined that bone mar-row cell populations from athymic NCr-nu mice (H-2d) mediate strong veto cell activity without exposure to exogenous IL-2 in vitro. To examine mechanisms by which these naturally occurring veto cell populations in BM suppress precursor CTL (pCTL) responses, we used as a responding cell population in MLC, spleen cells of transgenic mice expressing at high frequency TCR specific for H-2 L(d) encoded Ag with stimulation by H-2d-expressing cells in culture. Flow cytometric analysis was performed by staining the responding MLC cell population with the mAb 1B2 specific for the transgene-encoded TCR and determined changes of 1B2+ T cells. Such experiments demonstrated that the anti-H-2d cytotoxic response by these cell populations was specifically suppressed by NCr-nu (H-2d) bone marrow, and that 1B2+ pCTL were in fact specifically deleted from the responding cell population by incubation with such naturally occurring veto cell populations expressing the appropriate target Ag. In addition, to further understand the interactions of pCTL and veto cells and possible contributions by the latter to peripheral tolerance, we evaluated the effect of cyclosporine A (CsA) on veto cell-mediated suppression of pCTL of the transgenic mice. CsA inhibited veto cell-mediated suppression of cytotoxic T cell responses, and this inhibition correlated with a lack of clonal deletion of pCTL by veto cells in the presence of CsA. Furthermore, CsA exerted its effect through pCTL and not through veto cells, indicating that pCTL may play an active role in their own deletion by veto cells. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,RM 4B17,BETHESDA,MD 20892. NR 44 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1992 VL 149 IS 5 BP 1539 EP 1547 PG 9 WC Immunology SC Immunology GA JJ890 UT WOS:A1992JJ89000009 PM 1387142 ER PT J AU ROBERTS, JL ABE, R SHORES, EW SINGER, A AF ROBERTS, JL ABE, R SHORES, EW SINGER, A TI EXPRESSION OF MLS DETERMINANTS IN MICE EXHIBITING THE SEVERE COMBINED IMMUNODEFICIENCY (SCID) MUTATION OR X-LINKED IMMUNODEFICIENCY (XID) DEFECT SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; LYMPHOCYTE-ACTIVATING DETERMINANTS; DENDRITIC CELLS; MONOCLONAL-ANTIBODY; B-CELLS; MLS DETERMINANTS; NEONATAL TOLERANCE; ANTIGEN RECEPTOR; MOUSE; GENE AB While Ig+ B cells appear to be the principal cell type expressing immunogenic minor lymphocyte stimulatory (Mls) determinants, both T cells and B cells are capable of mediating deletion of developing Mls-reactive thymocytes. In addition, levels of mouse mammary tumor proviral transcripts are increased after B or T cell stimulation, and expression of functional Mls determinants is augmented by activation of B cells. These findings suggest Mls determinants are present on B and T lymphocytes, and that activation of B and T cells augments Mls expression. In the present study, we wished to determine whether B and T cells were required for expression of Mls determinants by examining mice with severe combined immunodeficiency (SCID) containing no detectable Ig+ B cells or TCR+ T cells, as well as animals that expressed the X-linked immunodeficiency (xid) defect and lacked a subset of mature B cells. We found MlS(a)-reactive V-beta-6hi T cells were deleted from thymi of male (CBA/NxAKR/J)F1 xid mice, and that spleen cells from these animals stimulated anti-Mls(a) mixed lymphocyte responses by unprimed B10.BR spleen T cells. In addition, Mls(c)-reactive V-beta-3hi AKR/J thymocytes and spleen T cells were deleted in AKR/J --> SCID bone marrow chimeras, and spleen cells from SCID mice stimulated proliferation by an Mls(c)-specific T cell clone. These results demonstrate that both xid mice and SCID animals express Mls determinants that mediate deletion of developing, Mls-responsive thymocytes and stimulate proliferation of mature, Mls-reactive T cells. Hence, mature B cells and T cells are not essential for Mls expression. RP ROBERTS, JL (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892, USA. NR 49 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1992 VL 149 IS 5 BP 1577 EP 1582 PG 6 WC Immunology SC Immunology GA JJ890 UT WOS:A1992JJ89000014 PM 1506683 ER PT J AU DOHERTY, GM LANGE, JR LANGSTEIN, HN ALEXANDER, HR BURESH, CM NORTON, JA AF DOHERTY, GM LANGE, JR LANGSTEIN, HN ALEXANDER, HR BURESH, CM NORTON, JA TI EVIDENCE FOR IFN-GAMMA AS A MEDIATOR OF THE LETHALITY OF ENDOTOXIN AND TUMOR-NECROSIS-FACTOR-ALPHA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ISCHEMIA REPERFUSION INJURY; INTERFERON-GAMMA; PASSIVE-IMMUNIZATION; RECOMBINANT HUMAN; PROTECTS MICE; LIPOPOLYSACCHARIDE; TNF; INTERLEUKIN-1; CACHECTIN; BACTEREMIA AB Current evidence indicates that endogenously produced peptide cytokines, most notably TNF-alpha and IL-1, mediate the lethality of experimental endotoxemia. Because circulating serum levels of IFN-gamma can be detected soon after TNF-alpha and IL-1 in response to endotoxin, we investigated the role of IFN-gamma in endotoxin and TNF-alpha lethality. Specific neutralizing antibodies to murine TNF-alpha (anti-TNF-alpha-Ab) or murine IFN-gamma (anti-IFN-gamma-Ab) produced in our laboratory protected mice against the lethality of Escherichia coli endotoxin (LPS) administered 6 h later. Serum IFN-gamma-levels 2 h after i.v. LPS were lower in mice treated with anti-TNF-alpha Ab compared to mice that received nonimmune IgG (median <2.5 vs 3.0 U/ml P2 < 0.05). In contrast, serum TNF-alpha levels 1 h after i.v. LPS peaked more than fourfold higher in mice treated with anti-IFN-gamma-Ab compared to controls (median > 6400 vs 1405 pg/ml, p2 < 0.05). Doses of TNF-alpha (300-mu-g/kg) and IFN-gamma (50,000 U) which were well tolerated when given individually were synergistically lethal in combination (0% lethality vs 100% lethality, P2 < 0.001), and were associated with higher serum levels of IL-6 than with either cytokine alone. Anti-IFN-gamma Ab provided complete protection against exogenous human rTNF-alpha at the LD100 dose (1400-mu-g/kg, p2 < 0.001), and in fact prevented lethality at doses four- to fivefold greater than the LD100 human rTNF-alpha (up to 6000-mu-g/kg). We conclude that IFN-gamma is synergistic with TNF-alpha, is essential for the lethality of LPS and TNF-alpha, and may have modulating effects on the negative control of serum levels of TNF-alpha after LPS in mice. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NR 28 TC 268 Z9 271 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1992 VL 149 IS 5 BP 1666 EP 1670 PG 5 WC Immunology SC Immunology GA JJ890 UT WOS:A1992JJ89000027 PM 1506688 ER PT J AU MAKINO, M CHATTOPADHYAY, SK HARTLEY, JW MORSE, HC AF MAKINO, M CHATTOPADHYAY, SK HARTLEY, JW MORSE, HC TI ANALYSIS OF ROLE OF CD8+ T-CELLS IN RESISTANCE TO MURINE AIDS IN A/J MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; LEUKEMIA VIRUSES; INDUCTION; SUSCEPTIBILITY; INFECTION; RESPONSES AB The mixture of retroviruses termed LP-BM5 murine leukemia virus (MuLV) contains a replication-defective genome (BM5def), the crucial element for induction of murine AIDS (MAIDS), as well as helper B-tropic ecotropic and mink cell focus-forming MuLV. Among Fv-1b mouse strains, C57BL mice are sensitive to infection by these viruses and to development of MAIDS, but A/J mice are highly resistant to all viral components and to induction of disease. Inasmuch as previous genetic studies indicated a major role in susceptibility for the H-2D locus within the MHC, the effect of CD8+ T cells in A/J resistance to MAIDS was analyzed by depletion of this subset using mAb. A/J mice treated with anti-CD8 mAb beginning soon after inoculation with LP-BM5 MuLV developed disease within 5 wk after virus inoculation. Histopathologic and flow cytometry alteration of tissues and cells from the mAb-treated mice were identical to those seen in virus-infected MAIDS-sensitive strains, and assays for MuLV demonstrated high-level expression of ecotropic MuLV and integration of BM5def. Parallel studies of A/J mice treated with anti-CD4 mAb after infection revealed enhanced expression of ecotropic MuLV but no integration of BM5def, and no signs of MAIDS were detected. These observations indicate that CD8+ T cells are critical in the resistance of A/J mice to LP-BM5 MuLV replication and development of disease and suggest that CD4+ T cells play a role in regulation of ecotropic virus replication. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. RP MAKINO, M (reprint author), NATL INST HLTH,DEPT BLOOD PROD,2-10-35 KAMIOOSAKI,SHINAGAWA KU,TOKYO 141,JAPAN. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-72622] NR 20 TC 41 Z9 41 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1992 VL 149 IS 5 BP 1702 EP 1706 PG 5 WC Immunology SC Immunology GA JJ890 UT WOS:A1992JJ89000032 PM 1506689 ER PT J AU MAKINO, M SEI, Y ARORA, PK MORSE, HC HARTLEY, JW AF MAKINO, M SEI, Y ARORA, PK MORSE, HC HARTLEY, JW TI IMPAIRED CALCIUM MOBILIZATION IN CD4+ AND CD8+ T-CELLS IN A RETROVIRUS-INDUCED IMMUNODEFICIENCY SYNDROME, MURINE AIDS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN KINASE-C; SELECTIVE SIGNALING DEFECT; LEUKEMIA-VIRUS; LYMPHOCYTE-ACTIVATION; COSTIMULATORY SIGNAL; MONOCLONAL-ANTIBODY; C57BL/6 MICE; ANTIGEN; INDUCTION; PROLIFERATION AB After infection with LP-BM5 murine leukemia viruses, susceptible strains of mice develop a severe and progressive immunodeficiency disease, termed murine AIDS (MAIDS), features of which include markedly impaired T cell response to mitogens or specific Ag stimulation and decreased production of IL-2. Since an elevation of intracellular calcium concentration resulting from binding of Ag to the TCR is associated with IL-2 production, T cells from mice either uninfected or infected with LP-BM5 murine leukemia viruses were examined by a calcium mobilization assay. Both CD4+ and CD8+ T cells from infected mice manifested impaired calcium mobilization responses upon in vitro stimulation with anti-CD3 mAb or Con A. The abnormalities appeared early after virus inoculation and showed no difference in time course between subsets of T cells. Frequencies of prestimulation calcium-positive cells among both CD4+ and CD8+ cells in mice with MAIDS were significantly higher than those for uninfected mice. These abnormalities were associated with presence of the MAIDS-inducing defective virus genome, but were not induced by infection of mice genetically resistant to development of MAIDS or with nonpathogenic helper murine leukemia virus, a virus component that induces high spontaneous proliferation of T cells, even in MAIDS-resistant mice. C1 NIAID,IMMUNOPATHOL LAB,BLDG 7,ROOM 304,BETHESDA,MD 20892. NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-72622] NR 45 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1992 VL 149 IS 5 BP 1707 EP 1713 PG 7 WC Immunology SC Immunology GA JJ890 UT WOS:A1992JJ89000033 PM 1354680 ER PT J AU ROONEY, JF STRAUS, SE MANNIX, ML WOHLENBERG, CR BANKS, S JAGANNATH, S BRAUER, JE NOTKINS, AL AF ROONEY, JF STRAUS, SE MANNIX, ML WOHLENBERG, CR BANKS, S JAGANNATH, S BRAUER, JE NOTKINS, AL TI UV-LIGHT INDUCED REACTIVATION OF HERPES-SIMPLEX VIRUS TYPE-2 AND PREVENTION BY ACYCLOVIR SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ULTRAVIOLET-LIGHT; GENITAL HERPES; LATENT HERPES; INFECTIONS; LABIALIS; PATHOGENESIS; TRANSPLANT; INDUCTION; IMMUNITY; ROOT AB UV B light is a potent stimulus for inducing reactivation of latent herpes simplex virus (HSV) infections. Patients were enrolled in a double-blind placebo-controlled crossover trial to determine whether acyclovir can prevent UV light-induced HSV-2 recurrences. Twenty-four patients with a history of recurrent infection of perigenital sites (e.g., buttock, thigh) were exposed one to four times with 4 minimum erythema doses of UV light. Patients were given acyclovir 200 mg orally five times daily or matched placebo beginning 1 day before each exposure and continuing for 5 days after exposure. There were 13 UV-induced recurrences among 36 placebo treatments and 3 after 38 acyclovir treatments (P = .004). The mean time to recurrence (+/-SE) was 4.8 +/- 0.3 days. HSV-2 lesions developed primarily at the site of UV exposure. The cutaneous distribution and timing of UV-induced recurrences was consistent with a neural localization (dorsal root ganglia) of latent viral infection. This UV light model permits direct examination of events leading to HSV-2 recurrences in humans and can be used to evaluate approaches to prevention. C1 NIDR,ORAL MED LAB,BLDG 30,RM 121,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. NR 33 TC 18 Z9 18 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1992 VL 166 IS 3 BP 500 EP 506 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JK029 UT WOS:A1992JK02900006 PM 1323616 ER PT J AU ROILIDES, E UHLIG, K VENZON, D PIZZO, PA WALSH, TJ AF ROILIDES, E UHLIG, K VENZON, D PIZZO, PA WALSH, TJ TI NEUTROPHIL OXIDATIVE BURST IN RESPONSE TO BLASTOCONIDIA AND PSEUDOHYPHAE OF CANDIDA-ALBICANS - AUGMENTATION BY GRANULOCYTE COLONY-STIMULATING FACTOR AND INTERFERON-GAMMA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TUMOR-NECROSIS-FACTOR; RESPIRATORY BURST; MACROPHAGE; METABOLISM; RECEPTORS AB The effects of granulocyte colony-stimulating factor (G-CSF) and interferon-gamma (IFN-gamma) on the oxidative burst of neutrophils (PMNL) in response to blastoconidia and pseudohyphae of Candida albicans were assessed and compared with those in response to N-FMLP. G-CSF enhanced oxidative burst, as measured by superoxide production, in response to both FMLP and opsonized blastoconidia. The enhancement of oxidative burst in response to FMLP was significantly greater (P = .004) than that in response to blastoconidia (65% and 39%, respectively). G-CSF also enhanced oxidative burst in response to pseudohyphae. IFN-gamma enhanced oxidative burst in response to FMLP and opsonized blastoconidia by 53% and 50%, respectively. Moreover, IFN-gamma significantly enhanced oxidative burst in response to opsonized and nonopsonized hyphae by 86% and 65%, respectively. These results demonstrate that G-CSF and IFN-gamma enhance the oxidative burst of PMNL in response to both blastoconidia and pseudohyphae of C. albicans and suggest an immunomodulatory role of the two cytokines in the host defenses against this fungus. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,RM 13N240,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 15 TC 45 Z9 45 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1992 VL 166 IS 3 BP 668 EP 673 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JK029 UT WOS:A1992JK02900039 PM 1380052 ER PT J AU BERNEMAN, ZN GALLO, RC ABLASHI, DV FRENKEL, N KATSAFANAS, G KRAMARSKY, B BRUS, I AF BERNEMAN, ZN GALLO, RC ABLASHI, DV FRENKEL, N KATSAFANAS, G KRAMARSKY, B BRUS, I TI HUMAN HERPESVIRUS-7 (HHV-7) STRAIN JI - INDEPENDENT CONFIRMATION OF HHV-7 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID T-CELLS; IDENTIFICATION; VIRUS; HBLV C1 NCI,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. ADV BIOTECHNOL,COLUMBIA,MD. MT SINAI MED CTR,SCH MED,NEW YORK,NY 10029. RP BERNEMAN, ZN (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,RM 6A09,BETHESDA,MD 20892, USA. NR 11 TC 63 Z9 64 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1992 VL 166 IS 3 BP 690 EP 691 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JK029 UT WOS:A1992JK02900049 PM 1323628 ER PT J AU BERGER, R GARTNER, S RAPPERSBERGER, K FOSTER, CA WOLFF, K STINGL, G AF BERGER, R GARTNER, S RAPPERSBERGER, K FOSTER, CA WOLFF, K STINGL, G TI ISOLATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 FROM HUMAN EPIDERMIS - VIRUS-REPLICATION AND TRANSMISSION STUDIES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID NECROSIS FACTOR-ALPHA; POLYMERASE CHAIN-REACTION; LANGERHANS CELLS; HTLV-III; TRANSGENIC MICE; KAPOSIS-SARCOMA; SYNDROME AIDS; LYMPHOCYTE-T; HIV; INFECTION AB For a better understanding of the pathogenetic events operative in the cutaneous manifestations of human immunodeficiency virus type 1 (HIV-1) disease, we investigated whether epidermal cells (EC) from HIV-1 - seronegative persons can be infected with HIV-1 and, vice versa, whether HIV-1 can be rescued from the epidermis of HIV-1 - infected individuals. In a series of three experiments, we consistently found that exposure of EC from HIV-1 - seronegative donors to HIV-1 led to viral replication in these cells as evidenced by the detection of HIV-1 p24 in culture fluids. Because EC had been substantially enriched for Langerhans cells (LC) before being exposed to HIV-1, it is reasonable to assume that these CD1a+/CD4+/MHC class II+ antigen-presenting cells of the epidermis represented the actual targets of infection. This assumption is further strengthened by the observation that T cell-depleted cell suspensions from Langerhans cell histiocytosis (LCH) lesions could be productively infected with HIV-1. Conversely, co-culture of epidermal sheets from HIV-1 - seropositive individuals with mononuclear phagocytes (MNP) from HIV-1 - seronegative donors resulted, after 3 to 5 weeks, in the detection of HIV-1 p24 in 12 of 23 cases. immunocytochemical analysis, using a monoclonal antibody specific for p24, revealed the presence of HIV-1 in adherent MNP in three cocultures tested. in addition, cellular DNA from these cultures showed strong signals when hybridized to a HIV-1 - specific DNA probe. The further finding that two isolates examined exhibited different restriction enzyme patterns indicates that they are separate entities rather than contaminants. Transmission of these isolates to MNP, B- or T-cell lines resulted in cultures strongly positive for p24 and, in the case of H9 cells, for viral particles as detected by electron microscopy. Our results therefore strongly suggest that EC not only can serve as targets for HIV-1, but also can allow efficient virus replication and transmit HIV-1 to various cell types of the hematopoietic lineage. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP BERGER, R (reprint author), UNIV VIENNA,SCH MED,DEPT DERMATOL 1,DIV CUTANEOUS IMMUNOBIOL,ALSER STR 4,A-1090 VIENNA,AUSTRIA. NR 42 TC 41 Z9 41 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1992 VL 99 IS 3 BP 271 EP 277 DI 10.1111/1523-1747.ep12616619 PG 7 WC Dermatology SC Dermatology GA JL546 UT WOS:A1992JL54600005 PM 1512462 ER PT J AU GRIFFITHS, CEM ROSENTHAL, DS REDDY, AP ELDER, JT ASTROM, A LEACH, K WANG, TS FINKEL, LJ YUSPA, SH VOORHEES, JJ FISHER, GJ AF GRIFFITHS, CEM ROSENTHAL, DS REDDY, AP ELDER, JT ASTROM, A LEACH, K WANG, TS FINKEL, LJ YUSPA, SH VOORHEES, JJ FISHER, GJ TI SHORT-TERM RETINOIC ACID TREATMENT INCREASES INVIVO, BUT DECREASES INVITRO, EPIDERMAL TRANSGLUTAMINASE-K ENZYME-ACTIVITY AND IMMUNOREACTIVITY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CROSS-LINKED ENVELOPE; HUMAN SKIN; KERATINOCYTE TRANSGLUTAMINASE; SQUAMOUS DIFFERENTIATION; CORNIFIED ENVELOPE; GENE-EXPRESSION; PROTEIN; CELLS; PURIFICATION; LOCALIZATION AB Epidermal transglutaminase-K is believed to catalyze the covalent linking of loricrin and involucrin to form cross-linked (CE) envelopes. In normal skin, transglutaminase-K is expressed as a band immediately below the stratum corneum, whereas in psoriasis and healing skin its expression is considerably expanded throughout the suprabasal layers. We have investigated whether the hyperproliferative state induced by short-term application of topical retinoic acid is similarly characterized by an increase in transglutaminase-K enzyme activity and immunoreactivity. Retinoic acid (0.1% cream) or vehicle were applied to human skin and occluded for 4 d. Skin biopsies were obtained for measurement of transglutaminase-K and transglutaminase-C activity and immunoreactivity. For comparison, cultured normal human keratinocytes were incubated for 4 d in the presence of 1-mu-M retinoic acid and the subsequent transglutaminase-K activity and immunoreactivity measured. Transglutaminase-K activity was increased 2.8 times in retinoic acid compared to vehicle-treated skin (p < 0.005, n = 12) whereas there was no significant difference in transglutaminase-C activity. However, transglutaminase-K mRNA levels were not significantly different between retinoic acid- and vehicle-treated skin. In vehicle-treated skin, transglutaminase-K immunoreactivity was limited to a narrow, substratum corneal band, but was considerably expanded in a diffuse suprabasal pattern in retinoic acid - treated epidermis. In contrast, transglutaminase-K immunostaining was decreased and its enzymatic activity reduced sixfold in retinoic acid-treated keratinocytes (p < 0.01, n = 4). These results demonstrate that retinoic acid treatment in vivo, in contrast to in vitro, leads to not only increased transglutaminase-K protein expression but also increased enzymatic activity in the absence of detectable increases in mRNA levels. These data, taken with the previously reported lack of in vivo modulation of the differentiation markers keratins 1 and 10 by retinoic acid, indicate that certain aspects of keratinocyte terminal differentiation that are altered in vitro by retinoic acid do not occur in vivo in human skin. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP GRIFFITHS, CEM (reprint author), UNIV MICHIGAN,MED CTR,DEPT DERMATOL,1910 TAUBMAN CTR,ANN ARBOR,MI 48109, USA. RI Griffiths, Christopher/P-5448-2014 OI Griffiths, Christopher/0000-0001-5371-4427 NR 38 TC 30 Z9 30 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1992 VL 99 IS 3 BP 283 EP 288 DI 10.1111/1523-1747.ep12616626 PG 6 WC Dermatology SC Dermatology GA JL546 UT WOS:A1992JL54600007 PM 1355099 ER PT J AU RAPPERSBERGER, K ROOS, N STANLEY, JR AF RAPPERSBERGER, K ROOS, N STANLEY, JR TI IMMUNOMORPHOLOGICAL AND BIOCHEMICAL-IDENTIFICATION OF THE PEMPHIGUS-FOLIACEUS AUTOANTIGEN WITHIN DESMOSOMES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CELL-ADHESION MOLECULES; CONSTITUTIVE TRANSMEMBRANE GLYCOPROTEIN; NON-EPIDERMAL DESMOSOMES; AMINO-ACID-SEQUENCE; HUMAN AUTOANTIBODIES; MR-165000 DESMOGLEIN; CADHERIN FAMILY; FOGO SELVAGEM; HUMAN SKIN; VULGARIS AB Desmosomes are specialized domains of the plasma membrane that play a fundamental role in intercellular adhesion. This adhesive function is mediated at least in part by the cadherin homologous cell adhesion molecule (CAM) desmoglein (dg). Autoantibodies (aab) from patients with pemphigus foliaceous (pf), a blistering disease of the epidermis, have been shown by immunochemical methods to bind to desmoglein. However, the molecular localization of the binding sites of these antibodies, especially as it relates to the ultrastructure of the desmosomes, has not been definitively characterized. We therefore performed pre-embedding direct immunoelectron microscopy (IEM) on perilesional skin of patients with pf and post-embedding indirect IEM using sera from five patients with pf. We first confirmed by immunoprecipitation and immunoblotting that these sera bound dg. Both IEM methods showed that pf-aab exclusively bind to desmosomes. Double-labeling IEM of several other constitutive desmosomal proteins further suggests that most likely pf-aab bind to an extracellular domain of the transmembrane CAM dg. Our studies suggest one possible pathophysiologic mechanism for the clinical manifestations of pf: namely, that the binding of aab to an extracellular epitope of desmoglein might impair the adhesive properties of desmosomes mediated by dg and result in the loss of cell adhesion leading to acantholysis and blister formation. C1 UNIV OSLO,DEPT BIOL,ELECTRONMICROSCOP LABS BIOL SCI,OSLO 3,NORWAY. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. RP RAPPERSBERGER, K (reprint author), UNIV VIENNA,DEPT DERMATOL 1,ALSERSTR 4,A-1090 VIENNA,AUSTRIA. NR 52 TC 63 Z9 63 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1992 VL 99 IS 3 BP 323 EP 330 DI 10.1111/1523-1747.ep12616659 PG 8 WC Dermatology SC Dermatology GA JL546 UT WOS:A1992JL54600014 PM 1512469 ER PT J AU COHEN, PJ KATZ, SI AF COHEN, PJ KATZ, SI TI CULTURED HUMAN LANGERHANS CELLS PROCESS AND PRESENT INTACT PROTEIN ANTIGENS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID DENDRITIC CELLS; T-CELL; LYMPHOCYTE-T; PERIPHERAL-BLOOD; IA MOLECULES; INVITRO; CLONES; REQUIREMENTS; STIMULATION; EXPRESSION AB Epidermal Langerhans cells (LC) undergo profound phenotypic and functional alterations when cultured for 2 to 3 d. To determine whether the in vitro culture of human LC modulates their capacity to process and present intact protein antigens, we compared the ability of freshly isolated LC (fLC) and cultured LC (cLC) to stimulate in vitro T-cell proliferative responses to recall antigens. We found that human fLC and cLC were able to process and present recall antigens to primed T cells, inducing significant proliferative responses. For tetanus toxoid and Candida albicans extract, T-cell proliferative responses at 6 d to antigen-pulsed fLC were slightly greater than responses to antigen-pulsed cLC. For live influenza A virus, the T-cell responses induced by antigen-pulsed cLC were comparable or slightly greater compared with fLC. Allogeneic T-cell proliferation for both LC preparations were also comparable. The exogenous pathway of antigen processing was demonstrated by chloroquine inhibition. C1 NCI,DERMATOL BRANCH,BLDG 10 ROOM 12N238,BETHESDA,MD 20892. NR 45 TC 26 Z9 26 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1992 VL 99 IS 3 BP 331 EP 336 DI 10.1111/1523-1747.ep12616663 PG 6 WC Dermatology SC Dermatology GA JL546 UT WOS:A1992JL54600015 PM 1512470 ER PT J AU LINDERS, JTM DECOSTA, BR GRAYSON, NA RICE, KC AF LINDERS, JTM DECOSTA, BR GRAYSON, NA RICE, KC TI SYNTHESIS OF UNLABELED AND TRITIUM LABELED 4-ISOTHIOCYANATO-1-(1-PHENYLCYCLOHEXYL)PIPERIDINE (FOURPHIT), TOOLS FOR THE STUDY OF THE DOPAMINE REUPTAKE COMPLEX SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE DOPAMINE REUPTAKE COMPLEX; COCAINE; AFFINITY LABEL; AUTORADIOGRAPHY; TRITIUM LABELED 4-ISOTHIOCYANATO-1-(1-PHENYLCYCLOHEXYL)PIPERIDINE; FOURPHIT ID PHENCYCLIDINE BINDING; METAPHIT; COCAINE; BRAIN; RECEPTORS; ASPARTATE; SITES AB The Synthesis of high specific activity tritium labelled 4-isothiocyanato-1-(1-phenylcyclohexyl)piperidine ([H-3]fourphit), a probe for the autoradiographic study of the dopamine reuptake complex, is described. An improved, facile synthesis of unlabelled fourphit in high overall yield is also presented. Detailed study of the interaction of unlabelled and tritium labelled fourphit with the dopamine reuptake complex may lead to a better understanding of the actions of cocaine. RP LINDERS, JTM (reprint author), NIDDKD,MED CHEM LAB,DRUG DESIGN & SYNTH SECT,BETHESDA,MD 20892, USA. NR 23 TC 2 Z9 2 U1 2 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD SEP PY 1992 VL 31 IS 9 BP 671 EP 683 DI 10.1002/jlcr.2580310906 PG 13 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA JK999 UT WOS:A1992JK99900005 ER PT J AU ORTALDO, JR WINKLERPICKETT, R KOPP, W KAWASAKI, A NAGASHIMA, K OKUMURA, K YAGITA, H BACH, FH AF ORTALDO, JR WINKLERPICKETT, R KOPP, W KAWASAKI, A NAGASHIMA, K OKUMURA, K YAGITA, H BACH, FH TI RELATIONSHIP OF LARGE AND SMALL CD3- CD56+ LYMPHOCYTES MEDIATING NK-ASSOCIATED ACTIVITIES SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE NATURAL KILLER CELLS; LYMPHOKINE-ACTIVATED KILLING; INTERLEUKIN-2; PORE-FORMING PROTEIN; BLT-ESTERASE ID NATURAL-KILLER-CELLS; INTERLEUKIN-2; PHENOTYPE; GRANULES; RECEPTOR; CD16 AB We have defined a population of CD3-, CD56+ small lymphocytes (SLs) that exhibit the same phenotype and lytic capacity as natural killer (NK) cells. NK cells characteristically express the surface markers CD16 and CD56, mediate non-major histocompatibility complex (MHC)-restricted lysis, and have been equated with CD3- large granular lymphocytes (LGLs). In the present study we extended the observation that CD3-, CD56+ SLs can mediate NK- and antibody-dependent cellular cytotoxicity activity by studying the activation signals and lytic mechanisms that might be utilized by CD3-, CD56+ SLs in comparison to CD3- CD56+ LGLs. Our results show that CD3- SLs, similar to CD3- LGLs, exhibited activated killing in response to interleukin-2 (IL-2). In addition, after IL-2 activation, the CD3- SLs exhibited morphologic changes, including increases in size and granularity, and both morphologically and phenotypically became virtually indistinguishable from CD3- LGLs. Similar to CD3- LGLs, CD3- SLs could be directly activated by IL-2 alone to secrete significant quantities of interferon-gamma (IFN-gamma) and to express IL-2 receptor (IL-2R) p55. Examination of serine esterases and pore-forming protein (PFP) demonstrated that these cells exhibited a cytoplasmic distribution of perforin, which, unlike that of CD3- LGLs, was not associated with dense cytoplasmic azurophilic granules. Serine esterase levels were similar. However, after IL-2 activation PFP was concentrated in dense cytoplasmic granules, similar or identical to the situation in CD3-, CD56+ LGLs. These CD3-, CD56+ subsets appear to represent a continuum of activated cells that might represent various states of maturation of NK cells. C1 JUNTENDO UNIV,SCH MED,DEPT IMMUNOL,TOKYO 113,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21701. UNIV MINNESOTA,DEPT LAB MED PATHOL,IMMUNOBIOL RES CTR,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT SURG,MINNEAPOLIS,MN 55455. RP ORTALDO, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DEPT CANC TREATMENT,BRMP,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-74102] NR 19 TC 14 Z9 14 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 1992 VL 52 IS 3 BP 287 EP 295 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA JQ371 UT WOS:A1992JQ37100007 PM 1381742 ER PT J AU GAGE, KL HOPLA, CE SCHWAN, TG AF GAGE, KL HOPLA, CE SCHWAN, TG TI COTTON RATS AND OTHER SMALL MAMMALS AS HOSTS FOR IMMATURE DERMACENTOR-VARIABILIS (ACARI, IXODIDAE) IN CENTRAL OKLAHOMA SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE ARACHNIDA; DERMACENTOR-VARIABILIS; SMALL MAMMALS; HOSTS ID AMERICAN DOG TICK; POPULATION-DYNAMICS; ECOLOGY; PATTERNS; VIRGINIA; AREA AB Eight species small mammals were evaluated as potential hosts for American dog ticks, Dermacentor variabilis (Say), in an upland, tallgrass prairie study site in central Oklahoma. Only hispid cotton rats, Sigmodon hispidus, and deer mice, Peromyscus maniculatus, were found to be important hosts for immature D. variabilis. Although D. variabilis larvae and nymphs frequently infested both cotton rats and deer mice, cotton rats were the most important host species for both immature stages in the study area. Cotton rats constituted 63.2% of the total 530 small mammals captured and were hosts to 85.2% of all larvae and 88.7% of all nymphs. Deer mice accounted for 19.8% of all small mammals captured and were hosts for 14.5% of the larvae and 10.8% of the nymphs recovered. The remaining small mammal species were hosts for < 1% of the immature ticks collected. Larval infestations peaked during summer, whereas summer and spring peaks were noted for the nymphal infestations. The relative importance of cotton rats and deer mice as hosts for immature ticks could be largely, but not completely, explained by cotton rats being more than three times as abundant as deer mice. Attachment site data indicated that differences in grooming behavior also might be partially responsible for the larger infestations observed on cotton rats. Other possible ecological and behavioral explanations of the heavy infestations observed on cotton rats are discussed. RP GAGE, KL (reprint author), NIAID,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. NR 44 TC 5 Z9 6 U1 0 U2 4 PU ENTOMOL SOC AMER PI LANHAM PA 9301 ANNAPOLIS RD, LANHAM, MD 20706 SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD SEP PY 1992 VL 29 IS 5 BP 832 EP 842 PG 11 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA JN291 UT WOS:A1992JN29100017 PM 1404263 ER PT J AU HIRAMATSU, Y BAUM, BJ AMBUDKAR, IS AF HIRAMATSU, Y BAUM, BJ AMBUDKAR, IS TI ELEVATION OF CYTOSOLIC [CA-2+] DUE TO INTRACELLULAR CA-2+ RELEASE RETARDS CARBACHOL STIMULATION OF DIVALENT-CATION ENTRY IN RAT PAROTID-GLAND ACINAR-CELLS SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE DIVALENT CATION ENTRY; MN-2+; [CA-2+]I ELEVATION; MUSCARINIC-CHOLINERGIC RECEPTOR; PAROTID ACINAR CELLS ID CALCIUM ENTRY; INOSITOL TRISPHOSPHATE; POSSIBLE MECHANISM; ENDOTHELIAL-CELLS; CA2+ ENTRY; RECEPTOR; POOL; 1,4,5-TRISPHOSPHATE; METABOLISM; PHOSPHATES AB This study examines the activation of divalent cation entry into rat parotid gland acinar cells by using Mn2+ as a Ca2+, surrogate cation. Following muscarinic-cholinergic stimulation of dispersed parotid acini with carbachol (10 muM), the onset of internal Ca2+ release (cytosolic [Ca2+], [Ca2+]i, increase) and the stimulation of Mn2+ entry (increase in fura2 quenching) are not simultaneously detected. [Ca2+]i elevation, due to intracellular release, is detected almost immediately following carbachol addition and peak [Ca2+]i increase occurs at 6.0 +/- 0.8 sec. However, there is an interval (apparent lag) between carbachol addition and the detection of stimulated Mn2+ entry. This apparent lag is decreased from 26 +/- 3.1 sec to 9.2 +/- 1.5 sec when external Mn2+ ([Mn2+]0) is increased from 12.5 to 500 muM. It is not decreased further with increase in [Mn2+]0 from 500 muM to 1 mm (9.8 +/- 2.1 sec), although both intracellular free Mn2+ and [Mn2+-fura2]/[fura2] increase. Thus, at [Mn2+]0 <500 muM, the observed lag time is partially due to a limitation in the magnitude of Mn2+ entry. Furthermore, neither peak [Ca2+]i nor the time required to reach peak [Ca2+]i is significantly altered by [Mn2+]0 (12.5 muM to 1 mm). At every [Mn2+]0 tested (i.e., 12.5 muM-1 mm), the apparent lag is significantly greater than the time required to reach peak [Ca2+]i. However, when carbachol stimulation of the [Ca2+]i increase is attenuated by loading the acini with the Ca2+ chelator, 2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA), there is no detectable lag in carbachol stimulation of Mn2+ entry (with 1 mm [Mn2+]0). Importantly, in BAPTA-loaded acini, carbachol stimulates Mn2+ entry via depletion of the internal Ca2+ pool and not via direct activation of other divalent cation entry mechanisms. Based on these results, we suggest that the apparent lag in the detection of carbachol stimulation of Mn2+ entry into parotid acinar cells is due to a retardation of Mn2+ entry by the initial increase in [Ca2+]i, due to internal release, which most likely occurs proximate to the site of divalent cation entry. RP HIRAMATSU, Y (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892, USA. NR 35 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD SEP PY 1992 VL 129 IS 3 BP 277 EP 286 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA JQ042 UT WOS:A1992JQ04200005 PM 1433279 ER PT J AU DEJONG, J VIRKKUNEN, M LINNOILA, M AF DEJONG, J VIRKKUNEN, M LINNOILA, M TI FACTORS ASSOCIATED WITH RECIDIVISM IN A CRIMINAL POPULATION SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID IMPULSIVE FIRE SETTERS; GLUCOSE-TOLERANCE TEST; VIOLENT OFFENDERS; HABITUALLY VIOLENT; AMINE METABOLITES; AGGRESSION; BEHAVIOR; PERSONALITY; INTELLIGENCE; ALCOHOLISM AB The present study is a follow-up of a sample of 348 men convicted of manslaughter, attempted manslaughter, or arson who were released from incarceration. Multiple factors assessed at the time of incarceration, including demographic, behavioral, family history, and biochemical variables, and psychiatric diagnoses were used in an attempt to discriminate between those who became recidivists during the follow-up period and those who did not. Violent recidivism was most strongly associated (sensitivity of 90%) with impulsivity of the original crime in killers and attempted killers; for arsonists, having made a suicide attempt, was the strongest predictor (68% sensitivity). For predictive purposes, both single factor associations and multiple entries into discriminant analysis produced too many false-positives, i.e., the high rate of false designation as recidivist remained a problem. C1 NIAA,DIV INTRAMURAL CLIN & BIOL RES,BETHESDA,MD. UNIV HELSINKI,DEPT PSYCHIAT,DIV FORENS PSYCHIAT,SF-00100 HELSINKI 10,FINLAND. NR 44 TC 48 Z9 48 U1 3 U2 13 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD SEP PY 1992 VL 180 IS 9 BP 543 EP 550 DI 10.1097/00005053-199209000-00001 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JP478 UT WOS:A1992JP47800001 PM 1522403 ER PT J AU SCUPI, BS MASER, JD UHDE, TW AF SCUPI, BS MASER, JD UHDE, TW TI THE NATIONAL-INSTITUTE-OF-MENTAL-HEALTH PANIC QUESTIONNAIRE - AN INSTRUMENT FOR ASSESSING CLINICAL CHARACTERISTICS OF PANIC DISORDER SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID LONGITUDINAL COURSE; ANXIETY DISORDERS; MAJOR DEPRESSION; SUICIDE ATTEMPTS; AGORAPHOBIA; INTERVIEW; SYMPTOMS; RELIABILITY; ILLNESS; ATTACKS AB This paper introduces a new self-report inventory, the NIMH Panic Questionnaire (NIMH PQ), for obtaining and quantifying comprehensive information about the clinical characteristics of panic disorder in patients with previously diagnosed or suspected illness. Fifty-two patients who met DSM-III-R criteria for panic disorder completed the NIMH PQ; their responses were compared with data derived from 16 similar or identical questions on the Schedule for Affective Disorders and Schizophrenia modified for anxiety disorders. There were no significant differences between the two instruments on 15 of the 16 (93.7%) items tested. The one exception revealed a greater proportion of patients versus physicians endorsing "spontaneous" panic, and a nonsignificant trend for physicians over patients endorsing anticipatory anxiety with greater frequency. The NIMH PQ offers a potentially useful clinical and research tool in the assessment of patients with known or suspected panic disorder. C1 NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BLDG 10,BETHESDA,MD 20892. NIMH,DIV CLIN RES,MOOD ANXIETY & PERSONAL DISORDERS RES BRANCH,BETHESDA,MD 20892. NR 35 TC 17 Z9 17 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD SEP PY 1992 VL 180 IS 9 BP 566 EP 572 DI 10.1097/00005053-199209000-00004 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JP478 UT WOS:A1992JP47800004 PM 1522405 ER PT J AU SUN, Y DEIBLER, GE SOKOLOFF, L SMITH, CB AF SUN, Y DEIBLER, GE SOKOLOFF, L SMITH, CB TI DETERMINATION OF REGIONAL RATES OF CEREBRAL PROTEIN-SYNTHESIS ADJUSTED FOR REGIONAL DIFFERENCES IN RECYCLING OF LEUCINE DERIVED FROM PROTEIN-DEGRADATION INTO THE PRECURSOR POOL IN CONSCIOUS ADULT-RATS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE BRAIN; AMINO ACID RECYCLING; LEUCINE; ACID-SOLUBLE AMINO ACID POOLS ID GLUCOSE-UTILIZATION; SYNTHESIS INVIVO; AMINO-ACIDS; BRAIN; METHIONINE AB The quantitative autoradiographic L-[1-C-14]leucine method for the determination of regional rates of cerebral protein synthesis in vivo takes into account recycling of unlabeled leucine derived from protein degradation into the precursor pool for protein synthesis. We have evaluated the degree of recycling by measuring the ratio of the apparent steady-state leucine specific activity in the precursor amino acid pool (tRNA-bound leucine) to that in the arterial plasma. In the whole brain of the conscious rat this ratio (lambda(WB)) equals 0.58. The equivalent ratio for leucine in the acid-soluble pool in whole brain (PSI(WB)) is 0.49. A first-degree polynomial equation for lambda(WB) as a function of PSI(WB) was fitted from paired determinations. To determine the degree of recycling in local regions of the brain, we have measured in individual brain regions (i) PSI(i) and calculated lambda(i) assuming that the fitted equation also applies to these localized regions. Our results indicate that the degree of recycling into the precursor pool does vary regionally; lambda(i) in the individual regions varies from 0.62 in the hypoglossal nucleus to 0.50 in the globus pallidus. Local rates of protein synthesis were then determined by the autoradiographic technique with regional corrections for recycling of unlabeled leucine. Rates of leucine incorporation into protein averaged 6.1 nmol/g of tissue/min in the brain as a whole, with the rates in gray matter about twice those in white matter. C1 NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A-05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 24 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1992 VL 59 IS 3 BP 863 EP 873 DI 10.1111/j.1471-4159.1992.tb08324.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JJ442 UT WOS:A1992JJ44200008 PM 1494912 ER PT J AU SUH, HH MAR, EC HUDSON, PM MCMILLIAN, MK HONG, JS AF SUH, HH MAR, EC HUDSON, PM MCMILLIAN, MK HONG, JS TI EFFECTS OF [SAR(1)]ANGIOTENSIN-II ON PROENKEPHALIN GENE-EXPRESSION AND SECRETION OF [MET(5)]ENKEPHALIN IN BOVINE ADRENAL-MEDULLARY CHROMAFFIN CELLS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE [SAR(1)]ANGIOTENSIN-II; PROENKEPHALIN GENE; [MET(5)]ENKEPHALIN; BOVINE ADRENAL MEDULLARY CHROMAFFIN CELLS ID A MESSENGER-RNA; ANGIOTENSIN-II; BINDING-SITES; ENKEPHALIN; RECEPTOR; RELEASE; CATECHOLAMINES; BIOSYNTHESIS; PEPTIDES AB We have studied the effect of [Sar1]angiotensin II [S1-AII; a degradation-resistant analogue of angiotensin II (AII)] on the release of [Met5]enkephalin (ME) and proenkephalin A (proENK) gene expression. Short-term (15-min to 1-h) stimulation of bovine adrenal medullary chromaffin (BAMC) cells with S1-AII at concentrations from 0.1 to 100 nM had no significant effect on secretion of ME, whereas high concentrations of S1-AII (3 to 100-mu-M) produced a concentration-dependent increase in the concentration of ME in the incubation media. In contrast, long-term (3- to 24-h) stimulation with low concentrations (0.1 nM-1-mu-M) of S1-AII increased the secretion of ME in a concentration-dependent manner (EC50 = 1 nM). The intracellular level of ME was not changed by long-term treatment with S1-AII (100 nM). In addition to increased ME secretion, long-term (24-h) stimulation with S1-AII increased the expression of proENK mRNA in a concentration-dependent manner (EC50 = 4 nM). Losartan {2-n-butyl-4 chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)-methyl]imidazole potassium salt, a type 1 AII receptor antagonist) inhibited these effects, whereas PD123319 (50-mu-M, a type 2 AII receptor antagonist) was inactive. Our results suggest that AII in BAMC cells exerts a major effect on the long-term regulation of expression of proENK mRNA and secretion of ME. These effects appear to be mediated by type 1-like AII receptors. C1 NIEHS,NEUROPHARMACOL SECT,MOLEC & INTEGRATIVE NEUROSCI LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 32 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1992 VL 59 IS 3 BP 993 EP 998 DI 10.1111/j.1471-4159.1992.tb08340.x PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JJ442 UT WOS:A1992JJ44200024 PM 1494921 ER PT J AU BURNET, PWJ MEFFORD, IN SMITH, CC GOLD, PW STERNBERG, EM AF BURNET, PWJ MEFFORD, IN SMITH, CC GOLD, PW STERNBERG, EM TI HIPPOCAMPAL 8-[H-3]HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN BINDING-SITE DENSITIES, SEROTONIN RECEPTOR (5-HT(1A)) MESSENGER-RIBONUCLEIC-ACID ABUNDANCE, AND SEROTONIN LEVELS PARALLEL THE ACTIVITY OF THE HYPOTHALAMOPITUITARY ADRENAL AXIS IN RAT SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE HIPPOCAMPUS; SEROTONIN; SEROTONIN 5-HT(1A) RECEPTOR; HYPOTHALAMOPITUITARY; ADRENAL AXIS; FISCHER F344/N; LEWIS ID CORTICOTROPIN-RELEASING HORMONE; LEWIS RATS; 5-HYDROXYTRYPTAMINE; ACTIVATION; SECRETION; BRAIN; CORTICOSTERONE; ANTAGONISTS; EXPRESSION; DEPRESSION AB We have previously demonstrated that susceptibility of the Lewis rat to inflammatory disease, compared with the relatively resistant Fischer F344/N rat, is related to a hyporesponsive hypothalamopituitary-adrenal axis to inflammatory and other stress mediators. Because serotonin (5-HT) and the 5-HT1A receptor are important stimulators of this axis, we have investigated the levels of 8-[H-3]-hydroxy-2,3-(di-n-propylamino)tetralin binding sites, 5-HT1A mRNA, 5-HT, and 5-hydroxyindoleacetic acid in various brain regions of Lewis, outbred Harlan Sprague Dawley, and Fischer F344/N rats. Lewis rats expressed significantly fewer hippocampal and frontal cortical 8-[H-3]hydroxy-2,3-(di-ni-propylamino)tetralin binding sites and less 5-HT1A mRNA than Harlan Sprague Dawley and Fischer F344/N rats. Adrenalectomy increased the number of 8-[H-3]hydroxy-2,3-(di-n-propylamino)tetralin binding sites and 5-HT1A mRNA expression in the hippocampus of all three strains. Levels of hippocampal 5-HT in Fischer F344/N rats were significantly greater than levels detected in the same regions from Lewis and Harlan Sprague Dawley rats. Hypothalamic 5-HT and 5-hydroxyindoleacetic acid levels in Harlan Sprague Dawley rats were higher than the same area from the other two strains. Adrenalectomy increased the levels of 5-hydroxyindoleacetic acid in the hypothalamus of all three strains. We conclude that hippocampal 5-HT1A receptor densities and 5-HT levels in the rat parallel the activity and responsiveness of the hypothalamopituitary-adrenal axis. C1 NIMH,CLIN EPIDEMIOL BRANCH,NEUROENDOCRINE IMMUNOL & BEHAV UNIT,BLDG 10,ROOM 3S-231,BETHESDA,MD 20892. NR 33 TC 73 Z9 74 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1992 VL 59 IS 3 BP 1062 EP 1070 DI 10.1111/j.1471-4159.1992.tb08348.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JJ442 UT WOS:A1992JJ44200032 PM 1379629 ER PT J AU HEYES, MP BREW, BJ SAITO, K QUEARRY, BJ PRICE, RW LEE, K BHALLA, RB DER, M MARKEY, SP AF HEYES, MP BREW, BJ SAITO, K QUEARRY, BJ PRICE, RW LEE, K BHALLA, RB DER, M MARKEY, SP TI INTERRELATIONSHIPS BETWEEN QUINOLINIC ACID, NEUROACTIVE KYNURENINES, NEOPTERIN AND BETA-2-MICROGLOBULIN IN CEREBROSPINAL-FLUID AND SERUM OF HIV-1-INFECTED PATIENTS SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE QUINOLINIC ACID; KYNURENIC ACID; L-TRYPTOPHAN; L-KYNURENINE; INDOLEAMINE-2,3-DIOXYGENASE; PTERINE; BETA-2-MICROGLOBULIN; NMDA RECEPTOR; AIDS DEMENTIA COMPLEX; INTERFERON-GAMMA ID HUMAN-IMMUNODEFICIENCY-VIRUS; INDOLEAMINE 2,3-DIOXYGENASE ACTIVITY; INFECTED RHESUS MACAQUES; GAMMA-INTERFERON; TRYPTOPHAN DEGRADATION; HIV-1 INFECTION; VIRAL STATUS; HUMAN-CELLS; RAT-BRAIN; INDUCTION AB Quinolinic acid (QUIN) is an neurotoxic N-methyl-D-aspartate receptor agonist and an L-tryptophan metabolite of the kynurenine pathway. Increased concentrations of QUIN occur in both cerebrospinal fluid (CSF) and blood of patients infected with human immunodeficiency virus (HIV)-1, particularly those with neurologic disturbances. In the present study of HIV-1 infected patients in Walter Reed stages 4, 5 and 6, reductions in L-tryptophan accompanied proportional increases in L-kynurenine and QUIN in both serum and CSF. Further, close inter-correlations exist between QUIN kynurenic acid and L-kynurenine with both beta-2-microglobulin and neopterin in CSF and serum. These correlations support the hypotheses that the kynurenine pathway is activated in association with inflammation and induction of indoleamine-2,3-dioxygenase. There were no relationships between CSF QUIN, L-kynurenine or kynurenic acid with the ratio of serum: CSF albumin concentrations, which indicates that the increases in CSF QUIN, L-kynurenine or kynurenic acid were not dependent on a breakdown of the blood-brain barrier. Kynurenic acid is also a kynurenine pathway metabolite that can attenuate the excitotoxic effects of QUIN when present in higher molar concentrations. While CSF kynurenic acid levels were increased in HIV-1-infected patients, the magnitude of the increases were smaller than those of QUIN and the molar concentrations of kynurenic acid were consistently lower than QUIN by at least one order of magnitude. We conclude that immune activation increases the levels of neuroactive kynurenines within the central nervous system of HIV-1-infected patients secondary to activation of indoleamine-2,3-di-oxygenase. C1 MEM SLOAN KETTERING CANC CTR,DEPT CHEM,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,NEW YORK,NY 10021. NIH,DEPT NUCL MED,BETHESDA,MD 20892. RP HEYES, MP (reprint author), NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BLDG 10,ROOM 3D40,BETHESDA,MD 20892, USA. RI Brew, Bruce/J-6513-2012 FU NINDS NIH HHS [NS-25701] NR 48 TC 111 Z9 112 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 1992 VL 40 IS 1 BP 71 EP 80 DI 10.1016/0165-5728(92)90214-6 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA JM581 UT WOS:A1992JM58100007 PM 1387655 ER PT J AU KAJANDER, KC BENNETT, GJ AF KAJANDER, KC BENNETT, GJ TI ONSET OF A PAINFUL PERIPHERAL NEUROPATHY IN RAT - A PARTIAL AND DIFFERENTIAL DEAFFERENTATION AND SPONTANEOUS DISCHARGE IN A-BETA AND A-DELTA PRIMARY AFFERENT NEURONS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SUPERFICIAL DORSAL HORN; ONGOING ACTIVITY; SCIATIC-NERVE; SPINAL-CORD; MONONEUROPATHY; CONSTRICTION; DISORDERS; BEHAVIOR; AXOTOMY; FIBERS AB 1. The activity of primary afferent axons was recorded in rats that had received a chronic constriction injury (CCI) to the common sciatic nerve. The CCI gives rise to a painful peripheral neuropathy that is characterized by allodynia, hyperalgesia, and, probably, spontaneous pain (or dysesthesia). In the majority of animals, these neuropathic pain symptoms begin 2 days postinjury; sciatic nerve afferents were examined just before and just after the time of symptom onset, at 1 and 3 days postinjury. 2. We used two stimulating electrodes, one proximal to the injury and the other distal, to activate the injured sciatic nerve while we recorded from individual primary afferent axons in microfilaments teased from the L4-L6 dorsal roots. Measurements of conduction velocities (calculated from the proximal electrode) and evaluation of conduction through the site of injury were made from 181 Abeta, 135 Adelta, and 60 C-fibers. 3. The percentage of axons that did not conduct through the injury site at 1 day postinjury was 85% for the Abeta fibers and 55% for the Adelta fibers, but only 9% for the C-fibers. By day 3, these percentages had increased to 89% for the Abeta fibers, 87% for the Adelta fibers, and 32% for the C-fibers. Some axons were activated from the distal stimulating electrode at currents >5- 10 times those required from the proximal electrodes, but their distally evoked responses did not have the longer latencies expected from a more distant site of activation. Control experiments confirmed that such high-threshold responses were due to current spread from the distal electrode to a site proximal to the nerve injury. 4. Spontaneous discharges were observed in 35% of Abeta fibers, 15% of Adelta fibers, and 3% of C-fibers (data from 1 and 3 days postinjury combined). Of the 55 Abeta fibers exhibiting spontaneous discharge, 89% did not conduct through the injury site; the same was true of 65% of the Adelta fibers (n = 20). Both of the two spontaneously discharging C-fibers conducted through the injury. The frequency of the spontaneous discharge of the myelinated fibers ranged from 10 to 50 Hz and was usually regular or bursting. 5. Intravenous administration of gallamine triethiodide (Flaxedil), a K+ channel blocker, either induced activity in previously silent fibers or increased the frequency of spontaneous activity in 50% (21/42) of Abeta fibers and 19% (3 /16) of Adelta fibers. There was no effect of systemic gallamine on any (0/4) of the C-fibers tested. 6. These data show that the abnormal pain sensations begin at about the same time as two abnormalities of primary afferent function. First, a large majority of Abeta and Adelta fibers become incapable of conducting impulses through the injury site, whereas a majority of the unmyelinated primary afferents conduct normally. Thus the injured nerve's peripheral territory is partially and differentially deafferented. Second, it is probable that as early as 1 day postinjury the spinal cord dorsal horn is bombarded by high levels of spontaneous discharge from many of the injured nerve's Abeta and Adelta afferents. It is possible that the high level of spontaneous input from myelinated afferents contributes to alterations in the somatosensory processing regions of the CNS. Moreover, it is probable that many spontaneously active Adelta afferents are nociceptors and that their activity results in spontaneous pain. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,9000 ROCKVILLE PK,BETHESDA,MD 20892. NR 51 TC 297 Z9 305 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1992 VL 68 IS 3 BP 734 EP 744 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA JP925 UT WOS:A1992JP92500008 PM 1331353 ER PT J AU WISE, SP DIPELLEGRINO, G BOUSSAOUD, D AF WISE, SP DIPELLEGRINO, G BOUSSAOUD, D TI PRIMATE PREMOTOR CORTEX - DISSOCIATION OF VISUOMOTOR FROM SENSORY SIGNALS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Note ID NEURONAL-ACTIVITY; VISUAL RESPONSES; ARM MOVEMENTS; MOTOR AREAS; MONKEY AB 1. If we assume adequate control for attention, memory, and stimulus location, a bona fide sensory response would be unaffected by whether a visuospatial stimulus instructs (1) one limb movement versus another or (2) limb movement versus a shift in spatial attention or memory. Two behavioral methods tested whether apparently sensory responses in the monkey's premotor cortex are strictly that, or, alternatively, whether they reflect the action instructed by a stimulus. 2. When an identical stimulus leads to two different responses, phasic discharge after a visuospatial stimulus is significantly, often dramatically, affected by the response. Similarly, premotor cortex neurons discharge more after a stimulus instructs a limb movement than after the same stimulus instructs a shift in spatial attention or memory. Thus, for the majority of premotor cortex neurons, the hypothesis that phasic poststimulus activity modulation represents a sensory response can be rejected. RP WISE, SP (reprint author), NIMH,NEUROPHYSIOL LAB,POB 289,POOLESVILLE,MD 20837, USA. RI Boussaoud, Driss/B-6932-2008; OI di Pellegrino, Giuseppe/0000-0001-7080-4758 NR 13 TC 38 Z9 38 U1 3 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1992 VL 68 IS 3 BP 969 EP 972 PG 4 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA JP925 UT WOS:A1992JP92500027 PM 1432062 ER PT J AU KARP, BPI JULIANO, DM BERMAN, KF WEINBERGER, DR AF KARP, BPI JULIANO, DM BERMAN, KF WEINBERGER, DR TI NEUROLOGIC OUTCOME OF PATIENTS WITH DORSOLATERAL PREFRONTAL LEUKOTOMY SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID TARDIVE-DYSKINESIA; FRONTAL LEUKOTOMY; SIGNS AB Few controlled studies of neurologic function in frontal leukotomy patients have been done. The authors compared neurologic examinations of patients who had bilateral leukotomies with those of psychiatric control subjects matched for age, diagnosis, and duration of illness. Cranial nerve dysfunction, abnormal involuntary movements, and primitive reflexes were common. No significant differences between the two patient groups were found. The leukotomized patients were less irritable than control subjects and had statistically higher seizure and death rates. Neurologic abnormalities are, thus, common in elderly chronic psychiatric patients. Surprisingly, patients with bilateral prefrontal leukotomy do not differ from well-matched psychiatric controls on most clinical tests of neurologic function. C1 ST ELIZABETH HOSP,NEUROSCI RES CTR,NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP KARP, BPI (reprint author), NINCDS,OFF CLIN DIRECTOR,BLDG 10,ROOM 5N-226,BETHESDA,MD 20892, USA. NR 24 TC 5 Z9 5 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1992 VL 4 IS 4 BP 415 EP 421 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JW450 UT WOS:A1992JW45000006 PM 1422168 ER PT J AU CRAWLEY, JN AF CRAWLEY, JN TI SUBTYPE-SELECTIVE CHOLECYSTOKININ RECEPTOR ANTAGONISTS BLOCK CHOLECYSTOKININ MODULATION OF DOPAMINE-MEDIATED BEHAVIORS IN THE RAT MESOLIMBIC PATHWAY SO JOURNAL OF NEUROSCIENCE LA English DT Article ID VENTRAL TEGMENTAL AREA; PEPTIDE-MONOAMINE COEXISTENCE; HYDROXYLASE MESSENGER-RNAS; CCK-B RECEPTORS; NUCLEUS-ACCUMBENS; TYROSINE-HYDROXYLASE; SUBSTANTIA-NIGRA; INSITU HYBRIDIZATION; H-3 MK-329; NEURONS AB Subtype-selective antagonists of the peripheral-type (CCKA) and the central-type (CCK-B) cholecystokinin (CCK) receptors were employed to determine the receptor subtype(s) mediating the modulatory actions of CCK on dopamine-induced changes in exploratory activity at three sites in the mesolimbic pathway of the rat. The CCK-A antagonist L-364,718 (10 ng) blocked CCK potentiation of dopamine-induced hyperlocomotion in the medial posterior nucleus accumbens. The CCK-B antagonist CI-988 (20 ng) blocked CCK inhibition of dopamine-induced hyperlocomotion in the anterior nucleus accumbens. The CCK-B antagonists CI-988 (20 ng) and L-365,260 (10 ng) blocked CCK potentiation of dopamine-induced hypolocomotion in the ventral tegmental area. These data indicate a CCK-B pharmacology in the cell body and anterior terminal field, and a CCK-A pharmacology in the posterior terminal field, of the mesolimbic dopamine pathway. Behavioral analyses using the selective CCK antagonists did not detect a contribution of endogenous CCK to exploratory locomotion. L-364,718 (10 ng), L-365,260 (10 ng), and CI-988 (20 ng or 2-mu-g), microinjected into the medial posterior nucleus accumbens, anterior nucleus accumbens, or ventral tegmental area, had no effect on baseline exploratory locomotion or on dopamine-induced changes in exploratory locomotion. Using a dark-induced hyperlocomotion paradigm, the CCK antagonists at these doses at these sites and intraperitoneally had no effect on the high levels of exploratory locomotor activity exhibited by the rats in the dark testing environment, or the lower levels of exploratory activity in the lighted environment. Endogenous CCK may not be released during dopamine-induced hyperlocomotion or dark-induced hyperlocomotion, or endogenous CCK may not contribute significantly to exploratory behaviors mediated through the mesolimbic dopamine pathway. Utilization of these potent, selective, nonpeptide CCK antagonists, with the doses, vehicles, and routes of administration developed in the present studies, will guide further investigations into the role of endogenous CCK in other facets of mesolimbic function. RP CRAWLEY, JN (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL UNIT,BLDG 10,ROOM 4N214,BETHESDA,MD 20892, USA. NR 68 TC 91 Z9 92 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1992 VL 12 IS 9 BP 3380 EP 3391 PG 12 WC Neurosciences SC Neurosciences & Neurology GA JN807 UT WOS:A1992JN80700007 PM 1527584 ER PT J AU LEHKY, SR SEJNOWSKI, TJ DESIMONE, R AF LEHKY, SR SEJNOWSKI, TJ DESIMONE, R TI PREDICTING RESPONSES OF NONLINEAR NEURONS IN MONKEY STRIATE CORTEX TO COMPLEX PATTERNS SO JOURNAL OF NEUROSCIENCE LA English DT Article ID INFERIOR TEMPORAL NEURONS; VISUAL-CORTEX; RECEPTIVE-FIELDS; NETWORK MODEL; MACAQUE; CELLS; ORGANIZATION; STIMULUS; CAT AB The overwhelming majority of neurons in primate visual cortex are nonlinear. For those cells, the techniques of linear system analysis, used with some success to model retinal ganglion cells and striate simple cells, are of limited applicability. As a start toward understanding the properties of nonlinear visual neurons, we have recorded responses of striate complex cells to hundreds of images, including both simple stimuli (bars and sinusoids) as well as complex stimuli (random textures and 3-D shaded surfaces). The latter set tended to give the strongest response. We created a neural network model for each neuron using an iterative optimization algorithm. The recorded responses to some stimulus patterns (the training set) were used to create the model, while responses to other patterns were reserved for testing the networks. The networks predicted recorded responses to training set patterns with a median correlation of 0.95. They were able to predict responses to test stimuli not in the training set with a correlation of 0.78 overall, and a correlation of 0.65 for complex stimuli considered alone. Thus, they were able to capture much of the input/output transfer function of the neurons, even for complex patterns. Examining connection strengths within each network, different parts of the network appeared to handle information at different spatial scales. To gain further insights, the network models were inverted to construct "optimal" stimuli for each cell, and their receptive fields were mapped with high-resolution spots. The receptive field properties of complex cells could not be reduced to any simpler mathematical formulation than the network models themselves. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. SALK INST BIOL STUDIES,COMPUTAT NEUROSCI LAB,LA JOLLA,CA 92093. NR 32 TC 33 Z9 33 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1992 VL 12 IS 9 BP 3568 EP 3581 PG 14 WC Neurosciences SC Neurosciences & Neurology GA JN807 UT WOS:A1992JN80700024 PM 1527596 ER PT J AU KOZAK, A NIKODIJEVIC, B YAVIN, E GUROFF, G AF KOZAK, A NIKODIJEVIC, B YAVIN, E GUROFF, G TI INTRACELLULAR CALCIUM LEVELS REGULATE THE ACTIONS OF NERVE GROWTH-FACTOR ON CALCIUM-UPTAKE IN PC12 CELLS SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE PC12; NERVE GROWTH FACTOR; NGF; CALCIUM; FLUO-3 ID FACTOR-INDUCED INCREASE; RAT PHEOCHROMOCYTOMA; SYMPATHETIC NEURONS; NEURITE OUTGROWTH; CHROMAFFIN CELLS; FIBER OUTGROWTH; LINE; HYDROLYSIS; SURVIVAL; CHANNELS AB The uptake of divalent cations and the intracellular concentration of calcium in PC12 cells were studied by flow cytometric analysis using the calcium-sensitive dye, Fluo-3, under a variety of conditions. In particular the actions of nerve growth factor were analyzed. The data show that nerve growth factor stimulates the uptake of divalent cations and increases the intracellular calcium levels of cells attached to collagen-coated plates. The data further indicate that nerve growth factor-dependent increases in the uptake of divalent cations become less pronounced as the intracellular concentration of calcium increases. Intracellular calcium levels increase upon detachment of the cells from the plates and also with increasing cell density. Studies on the uptake of calcium-45 confirmed the influence of intracellular calcium levels on nerve growth factor-stimulated calcium uptake. Thus, the effect of nerve growth factor on the uptake of divalent cations is dependent on the calcium levels in the cells, perhaps explaining why previous studies in this field have provided inconsistent results. C1 NICHHD, GROWTH FACTORS SECT, BETHESDA, MD 20892 USA. WEIZMANN INST SCI, DEPT NEUROBIOL, IL-76100 REHOVOT, ISRAEL. NR 33 TC 19 Z9 19 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP PY 1992 VL 33 IS 1 BP 30 EP 36 DI 10.1002/jnr.490330105 PG 7 WC Neurosciences SC Neurosciences & Neurology GA JL809 UT WOS:A1992JL80900004 PM 1453483 ER PT J AU WOLOZIN, B BACIC, M MERRILL, MJ LESCH, KP CHEN, C LEBOVICS, RS SUNDERLAND, T AF WOLOZIN, B BACIC, M MERRILL, MJ LESCH, KP CHEN, C LEBOVICS, RS SUNDERLAND, T TI DIFFERENTIAL EXPRESSION OF CARBOXYL TERMINAL DERIVATIVES OF AMYLOID PRECURSOR PROTEIN AMONG CELL-LINES SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Note DE ALZHEIMERS; LYSOSOME; CELL CULTURE; IMMUNOBLOT; PROCESSING; CATABOLISM ID ALZHEIMERS-DISEASE; INTERMEDIATE; FIBROBLASTS; RECEPTOR AB Understanding the pathway for amyloid precursor protein (APP) catabolism has become an important line of investigation. APP is a ubiquitous membrane bound protein that is rapidly cleaved at the membrane, yielding a secreted protein identical to protease nexin II and an internalized 11.5 kDa 100 residue C terminal derivative (CTD). The levels of CTDs in a variety of cell lines have been examined and were found to differ. Cell types associated with the pathology of Alzheimer's disease (AD), such as olfactory neuroblasts (ON) and cortical vascular endothelial cells, have higher levels of CTDs than lymphoblasts and melanoma cells. The mechanism of CTD catabolism appears to involve the lysosome because blockade of lysosomal but not endosomal or mitochondrial function results in increased levels of CTDs. Under these conditions, production of larger, amyloidogenic CTDs is also seen. In cells possessing higher levels of CTDs we find that the mechanism for production of amyloidogenic CTDs may involve the internalization of intact full-length APP. Thus, inhibition of the lysosomal system appears capable of generating amyloidogenic peptides. The amount of amyloidogenic peptides appears to vary among cell lines. Such variation may shed light on why amyloid accumulates around specific cell types such as vascular endothelial cells, neurons, and glia. Finally, disfunction of the lysosomal system may play a role in the pathogenesis of Alzheimer's disease. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NIDCD,BETHESDA,MD. RP WOLOZIN, B (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 20 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP PY 1992 VL 33 IS 1 BP 163 EP 169 DI 10.1002/jnr.490330121 PG 7 WC Neurosciences SC Neurosciences & Neurology GA JL809 UT WOS:A1992JL80900020 PM 1453480 ER PT J AU MEREDITH, RF KHAZAELI, MB LIU, TP PLOTT, G WHEELER, RH RUSSELL, C COLCHER, D SCHLOM, J SHOCHAT, D LOBUGLIO, AF AF MEREDITH, RF KHAZAELI, MB LIU, TP PLOTT, G WHEELER, RH RUSSELL, C COLCHER, D SCHLOM, J SHOCHAT, D LOBUGLIO, AF TI DOSE FRACTIONATION OF RADIOLABELED ANTIBODIES IN PATIENTS WITH METASTATIC COLON CANCER SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID I-131-LABELED MONOCLONAL-ANTIBODY; IMMUNE-RESPONSE; IRRADIATION; THERAPY; RADIOIMMUNOTHERAPY; PHARMACOKINETICS; DIAGNOSIS; CULTURES; GROWTH; CELLS AB Twelve patients with metastatic colon cancer were treated with I-131-chimeric B72.3 (IgG-4) at total doses of 28 or 36 mCi/m2 in two or three weekly fractions. Bone marrow suppression was the only significant side effect. The degree of bone marrow suppression adjusted for whole-body dose was modestly but statistically significantly (p = 0.04) less than that seen with identical doses given as a single infusion for the total dose of 36 mCi/m2. Nine of twelve patients developed an antibody response to ch B72.3, which altered the kinetics of radiolabeled antibody in four patients given a second course of therapy. One patient had a minor response that lasted 4 mo. Fractionation of this particular radiolabeled antibody at the dose schedule used produced a modest increase in the therapeutic window in regard to administered dose. C1 UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT NUCL MED,BIRMINGHAM,AL 35294. VET ADM MED CTR,BIRMINGHAM,AL 35233. UNIV NEBRASKA,OMAHA,NE 68182. AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965. NCI,BETHESDA,MD 20892. RP MEREDITH, RF (reprint author), UNIV ALABAMA,DEPT RADIAT ONCOL,CTR COMPREHENS CANC,WALLACE TUMOR INST 117,BIRMINGHAM,AL 35294, USA. FU NCI NIH HHS [CM87215]; NCRR NIH HHS [MO1 RR00032] NR 31 TC 74 Z9 75 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 1992 VL 33 IS 9 BP 1648 EP 1653 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JM032 UT WOS:A1992JM03200017 PM 1517839 ER PT J AU ROBINSON, MK AHN, MS ROUNDS, JD COOK, JA JACOBS, DO WILMORE, DW AF ROBINSON, MK AHN, MS ROUNDS, JD COOK, JA JACOBS, DO WILMORE, DW TI PARENTERAL GLUTATHIONE MONOESTER ENHANCES TISSUE ANTIOXIDANT STORES SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article ID GLUTATHIONE MONOETHYL ESTER; OXYGEN FREE-RADICALS; HEPATIC GLUTATHIONE; OXIDATIVE STRESS; INJURY; LIVER; TRANSPORT; BIOCHEMISTRY; INHIBITION; CYSTEINE AB Glutathione (GSH) is a potent endogenous antioxidant that protects major organs from oxidant injury. However, present nutrition regimens may inadequately support tissue stores of this tripeptide during critical illness. To determine whether GSH reserves can be enhanced in vivo with intravenous (IV) supplements, rats underwent central venous catheterization, were given chow and water ad libitum during a 2-day recovery period, and were then randomized to receive one of three treatments as an IV bolus: (1) dextrose, (2) glutathione (GSH), or (3) glutathione monoethyl ester. GSH monoethyl ester is transported into cells more easily than is GSH. Tissue and plasma samples were analyzed for GSH at 2 and 4 hours after drug administration. Liver, renal, and ileal mucosal GSH were significantly increased in the GSH-monoethyl ester rats compared with dextrose-treated animals. In addition, plasma GSH was dramatically increased after monoester injection. In contrast, GSH administration depressed liver GSH stores and did not significantly affect GSH concentration in the other organs analyzed. Plasma GSH concentration was elevated 2 hours after GSH administration. We conclude that: (1) the monoethyl ester of glutathione can be used in vivo to enhance tissue and plasma GSH concentration and (2) IV GSH administration does not significantly increase tissue GSH levels and may paradoxically depress hepatic GSH in normal rats. Because the malnourished and critically ill are likely to.have depleted GSH stores, nutrition strategies that include the provision of GSH monoester may lend additional support to those organs that are at risk for injury from oxygen free radicals during catabolic states. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT SURG,SURG METAB & NUTR LAB,THORN BLDG,BOSTON,MA 02115. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. FU NIGMS NIH HHS [5 P50 GM 36428, GM 07560-15, GM 42224-03] NR 44 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD SEP-OCT PY 1992 VL 16 IS 5 BP 413 EP 418 DI 10.1177/0148607192016005413 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA JT991 UT WOS:A1992JT99100003 PM 1433773 ER PT J AU SZALLASI, A LEWIN, NE BLUMBERG, PM AF SZALLASI, A LEWIN, NE BLUMBERG, PM TI IDENTIFICATION OF ALPHA-1-ACID GLYCOPROTEIN (OROSOMUCOID) AS A MAJOR VANILLOID BINDING-PROTEIN IN SERUM SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SENSORY-EFFERENT FUNCTION; PRIMARY AFFERENT NEURONS; DRUG-BINDING; CAPSAICIN; RESINIFERATOXIN; ANTAGONISTS; DISEASE; ALBUMIN AB We have used the vanilloid (capsaicin) receptor assay to search for modulators of binding activity. We report here that both capsaicin and its ultrapotent analog, resiniferatoxin (RTX), bind to the plasma protein alpha-1-acid glycoprotein (AGP) with high affinity (10.5 and 0.3-mu-M, respectively). AGP seems to be the dominant vanilloid (capsaicin/RTX) binding protein in serum. [H-3] RTX binding to AGP is inhibited by chlorpromazine and by Trisbutoxyethylphosphate, indicating that vanilloids compete for a well-characterized drug binding domain on the AGP molecule. The 35-fold difference in the affinity of AGP for RTX and capsaicin may result in differenceS in the pharmacodynamics and pharmacokinetics of these two compounds; the contribution of AGP binding to the unique spectra of action of RTX or to the marked species differences in vanilloid actions, however, remains to be determined. An important practical application of AGP is its inclusion in the [H-3]RTX binding assay utilizing sensory ganglion membranes to reduce nonspecific binding by up to 5-fold. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. NR 35 TC 66 Z9 66 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1992 VL 262 IS 3 BP 883 EP 888 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JN957 UT WOS:A1992JN95700001 PM 1527730 ER PT J AU TELLA, SR KORUPOLU, GR SCHINDLER, CW GOLDBERG, SR AF TELLA, SR KORUPOLU, GR SCHINDLER, CW GOLDBERG, SR TI PATHOPHYSIOLOGICAL AND PHARMACOLOGICAL MECHANISMS OF ACUTE COCAINE TOXICITY IN CONSCIOUS RATS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INTRAVENOUS COCAINE; SUDDEN-DEATH; GUINEA-PIGS; ABUSE; DOGS; INTOXICATION; MANAGEMENT; LETHALITY; SEIZURES; VASOCONSTRICTION AB In conscious rats, continuous i.v. infusion of cocaine (2 mg/kg/min) produced a marked increase in blood pressure, an initial moderate increase followed by a decrease in heart rate, tonic-clonic convulsions and, finally, a lethal episode of status epilepticus. No change in rectal temperature was observed. Infusion of cocaine methiodide (2 mg/kg/min), a quaternary derivative of cocaine, also produced a lethal episode of status epilepticus, but it was 6 times less potent than cocaine on a molar basis. In pentobarbital-anesthetized, spontaneously breathing rats, cocaine produced death by respiratory failure. Artificial ventilation of pentobarbital-anesthetized rats elevated the lethal dose of cocaine by 15-fold and these animals died of marked hypotension. In conscious rats, pretreatment with dl-, d- or l-propranolol or the alpha-2-selective adrenoceptor antagonist yohimbine enhanced the convulsive and lethal effects of cocaine. In contrast, the alpha-2-selective adrenoceptor agonist clonidine or the alpha-1-selective adrenoceptor antagonist prazosin attenuated these effects. Yohimbine antagonized the protective effect of clonidine. The nonselective alpha adrenoceptor antagonist phentolamine, the autonomic ganglionic blocker chlorisondamine and various calcium channel blockers had no effect on the convulsive or lethal doses of cocaine. The pressor response to cocaine was attenuated by calcium channel blockers, clonidine, phentolamine and dl- or l-propranolol, but not by d-propranolol. The pressor response to cocaine was abolished by chlorisondamine, reversed to a depressor response by prazosin and enhanced by yohimbine. The initial tachycardiac response to cocaine was reversed to bradycardia by dl- and l-propranolol, prazosin, yohimbine or high doses of the calcium channel blockers, but was unaffected by phentolamine, d-propranolol, clonidine or chlorisondamine. These results indicate that in spontaneously breathing animals, acute i.v. infusions of lethal doses of cocaine produce death primarily by central effects, namely by status epilepticus in conscious rats and by respiratory arrest in pentobarbital-anesthetized rats. In artificially ventilated, pentobarbital-anesthetized rats, however, cocaine produces death by effects on the cardiovascular system. In conscious rats, endogenous alpha-1 adrenoceptors exert a deleterious influence on cocaine-induced convulsive and lethal effects, whereas alpha-2 adrenoceptors provide protective influence. Propranolol appears to enhance cocaine-induced acute lethality through a mechanism independent of beta adrenoceptors. Calcium channel blockers appear ineffective in antagonizing cocaine's lethality. C1 GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,WASHINGTON,DC 20057. NIDA,ADDICT RES CTR,PRECLIN PHARMACOL LAB,BEHAV PHARMACOL & GENET SECT,BALTIMORE,MD 21224. NR 63 TC 46 Z9 46 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1992 VL 262 IS 3 BP 936 EP 946 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JN957 UT WOS:A1992JN95700009 PM 1527734 ER PT J AU AULAKH, CS HILL, JL LESCH, KP MURPHY, DL AF AULAKH, CS HILL, JL LESCH, KP MURPHY, DL TI FUNCTIONAL SUBSENSITIVITY OF 5-HYDROXYTRYPTAMINE1C OR ALPHA2 ADRENERGIC HETERORECEPTORS MEDIATING CLONIDINE-INDUCED GROWTH-HORMONE RELEASE IN THE FAWN-HOODED RAT STRAIN RELATIVE TO THE WISTAR RAT STRAIN SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NEURO-ENDOCRINE RESPONSES; SPRAGUE-DAWLEY RATS; DEPRESSED-PATIENTS; HEALTHY-SUBJECTS; META-CHLOROPHENYLPIPERAZINE; PROLACTIN SECRETION; 5-HT-1C RECEPTORS; CONSCIOUS RATS; CHOROID-PLEXUS; SEROTONIN AB Administration of various doses of clonidine increased plasma growth hormone levels. Pretreatment with the alpha-2 adrenergic antagonists, yohimbine and 1-(2-pyrimidyl)piperazine, completely blocked clonidine's effect on growth hormone levels. Pretreatment with the 5-hydroxytryptamine3 (5-HT3) receptor antagonist, MDL-72222, the 5-HT1A/5-HT2 antagonist, spiperone, and the mixed beta adrenergic/5-HT1B antagonists, /-propranolol and CGP361A, did not attenuate clonidine-induced increases in growth hormone levels. In contrast, pretreatment with the nonselective 5-HT1/2 antagonist, metergoline, and the 5-HT1C/5-HT2-selective antagonist, mesulergine, reduced clonidine-induced increases in growth hormone levels 81 to 87% without affecting clonidine-induced decreases in locomotor activity. Two other 5HT1C/5-HT2 antagonists, ritanserin and mianserin, also attenuated (47%) clonidine-induced increases in growth hormone levels. Pretreatment with the noradrenergic neurotoxin, DSP4, did not block clonidine's effect on growth hormone levels. Clonidine administration decreased locomotor activity in both the Fawn-Hooded and the Wistar rat strains to the same extent. On the other hand, clonidine administration failed to increase growth hormone levels in the Fawn-Hooded rat strain. These findings suggest that clonidine stimulates growth hormone secretion by activation of alpha-2 adrenergic heteroreceptors present on 5-HT nerve terminals which, in turn, enhance 5-HT activity via stimulation of postsynaptic 5-HT1C receptors to promote growth hormone releasing factor. Furthermore, either 5-HT1C receptors or alpha-2 adrenergic heteroreceptors or both are functionally subsensitive in the Fawn-Hooded rat strain relative to the Wistar rat strain. RP AULAKH, CS (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,BLDG 10,RM 3D-41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 57 TC 34 Z9 34 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1992 VL 262 IS 3 BP 1038 EP 1043 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JN957 UT WOS:A1992JN95700021 PM 1356149 ER PT J AU COMMENT, CE BLAYLOCK, BL GERMOLEC, DR POLLOCK, PL KOUCHI, Y BROWN, HW ROSENTHAL, GJ LUSTER, MI AF COMMENT, CE BLAYLOCK, BL GERMOLEC, DR POLLOCK, PL KOUCHI, Y BROWN, HW ROSENTHAL, GJ LUSTER, MI TI THYMOCYTE INJURY AFTER INVITRO CHEMICAL-EXPOSURE - POTENTIAL MECHANISMS FOR THYMIC ATROPHY SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ENDONUCLEASE ACTIVATION; IMMATURE THYMOCYTES; MURINE THYMOCYTES; CELL-DEATH; CALCIUM; APOPTOSIS; HEPATOCYTES; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; SUBPOPULATIONS; HOMEOSTASIS AB In addition to hepatic injury, thymic atrophy is a common observation in rodent subchronic toxicity studies. We have examined representative chemicals which produce thymic atrophy in rodents for their ability to cause direct thymocyte injury because the mechanism(s) responsible for these effects have not been determined. Although a number of the compounds examined failed to have any observable direct effect on thymocytes, others either inhibited lymphocyte proliferation or initiated cell death. In the latter group, thymocyte death was always preceded by increases in intracellular Ca++ and involved, to varying degrees, necrotic and apoptotic events. Apoptosis, as evidenced by cellular DNA cleavage into multiples of 180- 200-base pair oligonucleotides and partial cell protection by cycloheximide treatment, was most evident after treatment with acetaldehyde or dibutyltin dichloride. A number of compounds that produce thymic atrophy also inhibited T lymphocyte proliferation without evidence of cell death. Considering that many of the compounds tested failed to produce any evidence of direct thymocyte injury (i.e., necrosis, apoptosis or inhibition of cell proliferation), indirect mechanisms may also be involved in thymic atrophy and may target prothymocytes in the bone marrow, alter normal homing patterns or injure the thymic epithelium. Thus, it appears that a variety of mechanisms may be responsible for chemical-induced thymic atrophy and/or injury. C1 NIEHS,NATL TOXICOL PROGRAM,SYST TOXIC BRANCH,NEUROTOXICOL GRP,RES TRIANGLE PK,NC 27709. TAIHO PHARMACEUT CO,DRUG SAFETY LAB,TOSKUSHIMA,JAPAN. RP COMMENT, CE (reprint author), NIEHS,NATL TOXICOL PROGRAM,SYST TOXIC BRANCH,IMMUNOTOXICOL GRP,MD C1-04,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 37 TC 42 Z9 42 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1992 VL 262 IS 3 BP 1267 EP 1273 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JN957 UT WOS:A1992JN95700053 PM 1527729 ER PT J AU BRAHIM, JS GUCKES, AD RUDY, SF AF BRAHIM, JS GUCKES, AD RUDY, SF TI IMPLANT REHABILITATION IN ERDHEIM-CHESTER DISEASE - A CLINICAL REPORT SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Note RP BRAHIM, JS (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,PATIENT CARE & CLIN STUDIES SECT,BETHESDA,MD 20892, USA. NR 10 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD SEP PY 1992 VL 68 IS 3 BP 399 EP 401 DI 10.1016/0022-3913(92)90399-U PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JL247 UT WOS:A1992JL24700002 PM 1432751 ER PT J AU CASH, JM SWAIN, M DIBISCEGLIE, AM WILDER, RL CROFFORD, LJ AF CASH, JM SWAIN, M DIBISCEGLIE, AM WILDER, RL CROFFORD, LJ TI MASSIVE INTRAHEPATIC HEMORRHAGE FOLLOWING ROUTINE LIVER-BIOPSY IN A PATIENT WITH RHEUMATOID-ARTHRITIS TREATED WITH METHOTREXATE SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE RHEUMATOID ARTHRITIS; METHOTREXATE; LIVER BIOPSY; HEMORRHAGE ID THERAPY AB Massive intrahepatic hemorrhage occurred in a patient with rheumatoid arthritis (RA) after a routine liver biopsy done to assess possible methotrexate (MTX) hepatotoxicity. Major complications of liver biopsy occur about once in every 600 biopsies, and mortality from liver biopsy has been reported. Life threatening hepatic toxicity occurs rarely during low dose MTX administration, and it is unclear whether routine liver biopsies identify patients at high risk for these complications. Until the relative risks of liver biopsy and serious MTX liver toxicity are better defined, the use of routine liver biopsies should be recommended only after careful consideration of potential procedural complications in patients with RA treated with MTX. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD. NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. RI Crofford, Leslie/J-8010-2013 NR 19 TC 5 Z9 5 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 1992 VL 19 IS 9 BP 1466 EP 1468 PG 3 WC Rheumatology SC Rheumatology GA JN269 UT WOS:A1992JN26900031 PM 1433018 ER PT J AU NEWCOMER, S BALDWIN, W AF NEWCOMER, S BALDWIN, W TI DEMOGRAPHICS OF ADOLESCENT SEXUAL-BEHAVIOR, CONTRACEPTION, PREGNANCY, AND STDS SO JOURNAL OF SCHOOL HEALTH LA English DT Article ID UNITED-STATES; ABORTION; DISEASE AB The demographics of fertility-related behavior of youth ages 10-18 are reviewed. Data were collected from U.S. vital statistics, and birth rates, contraceptive use, sexual behavior, number and types of sexual partners, patterns of sexual initiation and sexual intercourse, and sexually transmitted diseases were examined. Despite data limitations, the demographic profile of adolescent sexual intercourse is striking. Age clearly is the single most important predictor of sexual debut. RP NEWCOMER, S (reprint author), NICHHD,DEMOG & BEHAV SCI BRANCH,BETHESDA,MD 20892, USA. NR 19 TC 27 Z9 27 U1 1 U2 4 PU AMER SCHOOL HEALTH ASSOC PI KENT PA PO BOX 708, KENT, OH 44240 SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD SEP PY 1992 VL 62 IS 7 BP 265 EP 270 PG 6 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA JR628 UT WOS:A1992JR62800003 ER PT J AU SIMONS, SS OSHIMA, H SZAPARY, D AF SIMONS, SS OSHIMA, H SZAPARY, D TI MODULATION OF THE AGONIST ACTIVITY OF ANTISTEROIDS BY A NOVEL CIS-ACTING ELEMENT SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 4TH INTERNATIONAL CONGRESS ON HORMONES AND CANCER CY SEP, 1991 CL AMSTERDAM, NETHERLANDS ID TRANSCRIPTION FACTORS INTERACT; TISSUE-CULTURE CELLS; RAT HEPATOMA-CELLS; GLUCOCORTICOID RECEPTORS; TYROSINE AMINOTRANSFERASE; ESTROGEN-RECEPTOR; DNA-BINDING; CYCLIC-AMP; CHLORAMPHENICOL ACETYLTRANSFERASE; DEXAMETHASONE 21-MESYLATE AB The amount of agonist activity displayed by the antiglucocorticoid dexamethasone mesylate (Dex-Mes) for the induction of tyrosine aminotransferase (TAT) in rat hepatoma cells is greater than for glutamine synthetase and varies over a period of weeks. This variation, which has been reproduced over a period of 40 h by changing the density of the cells, suggests the involvement of a trans-acting factor. The target of this proposed trans-acting factor has now been localized to the region between -3.9 to -2.9 of the rat TAT gene from experiments with cells that were stably transfected with hybrid TAT/CAT constructs. Deletion experiments with transiently transfected TAT/tk promoter/CAT constructs revealed that this entire activity could be conveyed by a 21 bp sequence of the TAT gene. Gel shift experiments support the binding of a factor(s) to this 21 bp sequence. Thus the activity of the antagonist Dex-Mes is relatively independent of steroid structure and is largely determined by the further interactions of a trans-acting factor with the cis-acting sequence. We call this novel sequence a glucocorticoid modulatory element. A model is advanced which accounts for almost all of the results concerning TAT induction by glucocorticoids, This same model may also be useful in explaining why the amount of agonist activity of most antisteroids varies, even for different genes within the same cell. RP SIMONS, SS (reprint author), NIDDK,LMCB,STEROID HORMONES SECT,BETHESDA,MD 20892, USA. NR 48 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD SEP PY 1992 VL 43 IS 1-3 BP 43 EP 55 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA JM324 UT WOS:A1992JM32400008 PM 1356017 ER PT J AU RONDINONE, CM BAKER, ME RODBARD, D AF RONDINONE, CM BAKER, ME RODBARD, D TI PROGESTINS STIMULATE THE DIFFERENTIATION OF 3T3-L1 PREADIPOCYTES SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID ADIPOSE PRECURSOR CELLS; LIPOPROTEIN-LIPASE ACTIVITY; INSULIN-RECEPTORS; STEROID-HORMONES; GLYCEROPHOSPHATE DEHYDROGENASE; ADIPOCYTE DIFFERENTIATION; GENE-EXPRESSION; PRIMARY CULTURE; MESSENGER-RNA; GROWTH-FACTOR AB The effect of progesterone on the differentiation of the 3T3-L1 preadipocytes was investigated and compared with other sex steroids (estradiol and testosterone), with cortisol, with the synthetic progestin R5020 and with the progestin/glucocorticoid antagonist RU38486. At 10(-8) M, progesterone stimulated the activity of glycerol-3-phosphate dehydrogenase and triglyceride deposition. Progesterone, R5020, cortisol, and RU38486 increased triglycerides about 2-fold at 10(-7) M. Only minimal effects were observed with testosterone and estradiol even at 10(-6) M. When the cells were cultured in presence of 10(-5) M metyrapone the effect of progesterone was unchanged, suggesting that the progesterone was not metabolized to a glucocorticoid. Progesterone, R5020 and RU38486 competed efficiently with [H-3]dexamethasone for the glucocorticoid receptor in 3T3-L1 cytosol. These results indicate a significant, reproducible dose-dependent effect of progestins on differentiation of the preadiocytes, which appears to be mediated via the glucocorticoid receptor. C1 NICHHD,THEORET PHYS BIOL LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,DEPT MED,0623B,LA JOLLA,CA 92093. OI Baker, Michael/0000-0003-4387-3269 NR 45 TC 32 Z9 32 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD SEP PY 1992 VL 42 IS 8 BP 795 EP 802 DI 10.1016/0960-0760(92)90087-Y PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA JN018 UT WOS:A1992JN01800002 PM 1525040 ER PT J AU HARFORD, TC BROOKS, SD AF HARFORD, TC BROOKS, SD TI CIRRHOSIS MORTALITY AND OCCUPATION SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID MEN AB Cirrhosis, the ninth leading cause of death in the United States, has been associated with abusive alcohol consumption patterns. Since the workplace serves as a major exposure variable for alcohol consumption over a significant portion of the lifecourse, and since heavy drinking has been shown to differ by type of occupation, this study examines the relationship between type of occupation and cirrhosis mortality. The California Occupational Mortality Study data set (1979 to 1981) provided the information on primary occupation and liver cirrhosis mortality. Crude and sex-specific mortality rates were calculated based on information from a 20% sample of the 1980 California census (included in the data set). Ninety-five percent confidence intervals were calculated around all rates to determine if any were significantly different from rates for the entire state. The findings uphold the view that an association exists between occupation and cirrhosis mortality. The highest mortality rates were found among persons with blue-collar type jobs (e.g., construction laborers and machinists) or jobs where alcohol was easily available (e.g., bartenders and waitresses). Future research needs to specify the factors associated with occupation that may promote the chronic heavy drinking that leads to cirrhosis. RP HARFORD, TC (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,ROOM 14C-26,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 13 TC 22 Z9 23 U1 0 U2 0 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD SEP PY 1992 VL 53 IS 5 BP 463 EP 468 PG 6 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA JK563 UT WOS:A1992JK56300009 PM 1405639 ER PT J AU WERKMAN, S JENSEN, PS AF WERKMAN, S JENSEN, PS TI RESOLVED - MILITARY FAMILY-LIFE IS HAZARDOUS TO THE MENTAL-HEALTH OF CHILDREN SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Discussion ID NUMBERS; RISK C1 NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,DIV CLIN RES,ROCKVILLE,MD 20857. RP WERKMAN, S (reprint author), GEORGETOWN UNIV,SCH MED,WASHINGTON,DC 20057, USA. NR 13 TC 9 Z9 9 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 1992 VL 31 IS 5 BP 984 EP 987 DI 10.1097/00004583-199209000-00029 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA JM584 UT WOS:A1992JM58400029 PM 1400134 ER PT J AU MASRIFRIDLING, GD TURNER, MLC AF MASRIFRIDLING, GD TURNER, MLC TI NECROLYTIC MIGRATORY ERYTHEMA WITHOUT GLUCAGONOMA SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter ID HEPATIC IMPAIRMENT; PATHOGENESIS; DERMATITIS; CLUE; ACID C1 NCI,DEPT DERMATOL,BETHESDA,MD 20892. RP MASRIFRIDLING, GD (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT DERMATOL,2150 PENN AVE NW,WASHINGTON,DC 20037, USA. NR 7 TC 13 Z9 13 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 1992 VL 27 IS 3 BP 486 EP 486 DI 10.1016/S0190-9622(08)80892-4 PG 1 WC Dermatology SC Dermatology GA JL250 UT WOS:A1992JL25000028 PM 1401295 ER PT J AU AKBASAK, A SUNARAKBASAK, B AF AKBASAK, A SUNARAKBASAK, B TI ONCOGENES - CAUSE OR CONSEQUENCE IN THE DEVELOPMENT OF GLIAL TUMORS SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Review DE ONCOGENE EXPRESSION; PROTOONCOGENE; TUMOR SUPPRESSOR GENE; CHROMOSOMAL ABERRATION; GLIOMA ID GROWTH-FACTOR RECEPTOR; SIMIAN SARCOMA-VIRUS; HUMAN-BRAIN-TUMORS; CENTRAL-NERVOUS-SYSTEM; C-FOS PROTEIN; THYROID-HORMONE RECEPTOR; TYROSINE KINASE-ACTIVITY; MALIGNANT HUMAN GLIOMAS; ASTROCYTOMA CELL-LINES; RAS GENE-PRODUCTS AB Recent developments in the field of oncogenes and growth stimulatory factors have provided limited but essential models in neuro-oncology. The observation in gliomas of platelet growth factor (PDGF)-like immunoreactivity fits with the autocrine secretion model, rising the possibility for the growth factor independence of the cancer cells. The discovery of the tumor suppressor genes, for which loss of function mutations are oncogenic as in the RB gene of the retinoblastoma and p53 gene, has introduced a new concept of oncogenesis which could be useful even in the cure of the neoplasms. Several oncogenes are amplified and/or expressed in brain tumors, some associated with polymorphism leading to abnormal protein products. Therefore, corresponding functions, such as production of deficient epidermal growth factor receptor (EGFR) encoded by erb-B, are impaired. Abnormal chromosomal patterns have been recognized in brain tumors and found mainly in chromosomes 7 and 22 on which oncogenes erb-B and sis are located, respectively. Location of proto-oncogenes, which are normally expressed in the brain, indicate that they share common distribution patterns mainly involving the cerebellum, hippocampus and olfactory bulbs. These proto-oncogenes may be regulated by physiological and pathological events. The concept of oncogene involvement in brain tumors must be extended to include the other factors such as G-proteins, growth factor receptors, membrane-associated and cytoplasmic protein kinases, which are all responsible for the control of the cell growth and their response to external signals including chemotherapeutic drugs. C1 NINCDS,CLIN NEUROSURG SECT,SURG NEUROL BRANCH,BETHESDA,MD 20892. NICHHD,ENDOCRINE PHYSIOL SECT,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 164 TC 26 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD SEP PY 1992 VL 111 IS 2 BP 119 EP 133 DI 10.1016/0022-510X(92)90060-X PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JQ379 UT WOS:A1992JQ37900001 PM 1331337 ER PT J AU LINEHAN, WM AF LINEHAN, WM TI DISTRIBUTION OF 486P 3/12-ANTIGEN, ABO(H) BLOOD-GROUP ANTIGEN AND T-ANTIGEN IN CYSTECTOMY SPECIMENS FROM PATIENTS WITH STAGE-T2 TRANSITIONAL CELL-CARCINOMA OF BLADDER - COMMENT SO JOURNAL OF UROLOGY LA English DT Editorial Material RP LINEHAN, WM (reprint author), NCI,UROL ONCOL SECT,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 1992 VL 148 IS 3 BP 805 EP 805 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA JL738 UT WOS:A1992JL73800017 ER PT J AU RODGERS, CH AF RODGERS, CH TI THE HISTORY OF RESEARCH TRAINING AND CAREER AWARDS IN UROLOGICAL SCIENCE SUPPORTED IN THE NATIONAL-INSTITUTE-OF-DIABETES-AND-DIGESTIVE-AND-KIDNEY-DISEASES SO JOURNAL OF UROLOGY LA English DT Article DE NATIONAL-INSTITUTES-OF-HEALTH; RESEARCH SUPPORT; GRANTS AND SUBSIDIES, RESEARCH AB Urology research and training grants were placed into a separate research program in 1979. Research emphasis and the context of training programs have changed from a focus on urolithiasis in the 1970s to a broader range of urological disorders in the 1980s. From 1977 to 1990, 49 applications were submitted by 47 applicants for research training/career development support and 39% of the applications were successful. From 1977 to 1987 medical doctors applying for research/career training had a 75% success rate in subsequent National Institutes of Health research grant applications, and basic scientists had a 67% success rate. Of the 33 former trainees supported on institutional training grants during the last 14 years 76% were medical doctors and 24% were basic scientists. From 1977 to 1987, no former medical doctors or basic scientists from institutional training grants have a record of applying to the National Institutes of Health for research grant support. The urology community needs to capitalize on the available opportunities to expand the training programs to increase the number of physician and urological research scientists. RP RODGERS, CH (reprint author), NIDDKD,DIV KIDNEY UROL & HEMATOL DIS,BETHESDA,MD, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 1992 VL 148 IS 3 BP 891 EP 893 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA JL738 UT WOS:A1992JL73800051 PM 1512850 ER PT J AU KANNO, H WOLFINBARGER, JB BLOOM, ME AF KANNO, H WOLFINBARGER, JB BLOOM, ME TI IDENTIFICATION OF ALEUTIAN MINK DISEASE PARVOVIRUS TRANSCRIPTS IN MACROPHAGES OF INFECTED ADULT MINK SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING ANTIBODY; HYBRIDIZATION PROBES; VIRAL REPLICATION; VIRUS-STRAINS; DNA; ENHANCEMENT; ANTIGEN; TISSUES; CELLS AB We examined Aleutian mink disease parvovirus (ADV) mRNA expression in lymph nodes of adult mink infected with ADV by Northern (RNA) blot and in situ hybridization. In Northern blot analysis, ADV transcripts were detected in the poly(A) RNA fraction extracted from mesenteric lymph nodes of two of five mink 10 days after intraperitoneal inoculation with the virulent Utah I strain of ADV. In strand-specific in situ hybridization, ADV DNA and mRNA were detected in some macrophagelike cells located in the medullary sinus in mesenteric lymph node sections from two of six infected mink by using biotinylated probes. In suspensions of lymph node cells, about 30% of the cells phagocytic for latex particles contained ADV DNA and about 1% of these cells contained ADV mRNA. In peritoneal exudate cells, about 20% of the macrophagelike cells contained ADV DNA and about 2% of these cells contained ADV mRNA. These results indicated that some macrophages in ADV-infected mink contained ADV mRNA and were target cells in ADV infection. C1 NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,HAMILTON,MT 59840. NR 35 TC 21 Z9 22 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1992 VL 66 IS 9 BP 5305 EP 5312 PG 8 WC Virology SC Virology GA JJ198 UT WOS:A1992JJ19800017 PM 1323697 ER PT J AU PHILLIPS, TR LAMONT, C KONINGS, DAM SHACKLETT, BL HAMSON, CA LUCIW, PA ELDER, JH AF PHILLIPS, TR LAMONT, C KONINGS, DAM SHACKLETT, BL HAMSON, CA LUCIW, PA ELDER, JH TI IDENTIFICATION OF THE REV TRANSACTIVATION AND REV-RESPONSIVE ELEMENTS OF FELINE IMMUNODEFICIENCY VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID STRUCTURAL GENE-EXPRESSION; VIRAL MESSENGER-RNA; VISNA VIRUS; TRANS-ACTIVATOR; NUCLEOTIDE-SEQUENCE; AMINO-ACIDS; TYPE-1; PROTEIN; HIV-1; RETROVIRUS AB Spliced messages encoded by two distinct strains of feline immunodeficiency virus (FIV) were identified. Two of the cDNA clones represented mRNAs with bicistronic capacity. The first coding exon contained a short open reading frame (orf) of unknown function, designated orf 2. After a translational stop, this exon contained the L region of the env orf. The L region resides 5' to the predicted leader sequence of env. The second coding exon contained the H orf, which began 3' to env and extended into the U3 region of the long terminal repeat. The in-frame splicing of the L and H orfs created the FIV rev gene. Site-directed antibodies to the L orf recognized a 23-kDa protein in infected cells. Immunofluorescence studies localized Rev to the nucleoli of infected cells. The Rev-responsive element (RRE) of FIV was initially identified by computer analysis. Three independent isolates of FIV were searched in their entirety for regions with unusual RNA-folding properties. An unusual RNA-folding region was not found at the Su-TM junction but instead was located at the end of env. Minimal-energy foldings of this region revealed a structure that was highly conserved among the three isolates. Transient expression assays demonstrated that both the Rev and RRE components of FIV were necessary for efficient reporter gene expression. Cells stably transfected with rev-deleted proviruses produced virion-associated reverse transcriptase activity only when FIV Rev was supplied in trans. Thus, FIV is dependent on a fully functional Rev protein and an RRE for productive infection. C1 SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. Scripps Res Inst, DEPT NEUROPHARMACOL, LA JOLLA, CA 92037 USA. NCI, DIV CANC BIOL & DIAG, MATH BIOL LAB, FREDERICK, MD 21701 USA. UNIV CALIF DAVIS, DEPT MED PATHOL, DAVIS, CA 95616 USA. RI Shacklett, Barbara/A-7288-2009 OI Shacklett, Barbara/0000-0002-7067-732X FU NIAID NIH HHS [R01AI25825, R01AI28580] NR 43 TC 98 Z9 100 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1992 VL 66 IS 9 BP 5464 EP 5471 PG 8 WC Virology SC Virology GA JJ198 UT WOS:A1992JJ19800035 PM 1323707 ER PT J AU LORI, F HALL, L LUSSO, P POPOVIC, M MARKHAM, P FRANCHINI, G REITZ, MS AF LORI, F HALL, L LUSSO, P POPOVIC, M MARKHAM, P FRANCHINI, G REITZ, MS TI EFFECT OF RECIPROCAL COMPLEMENTATION OF 2 DEFECTIVE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) MOLECULAR CLONES ON HIV-1 CELL TROPISM AND VIRULENCE SO JOURNAL OF VIROLOGY LA English DT Article ID FELINE LEUKEMIA-VIRUS; REVERSE-TRANSCRIPTASE; ENVELOPE GENE; HTLV-III; SOR GENE; MUTATIONAL ANALYSIS; ZIDOVUDINE AZT; POINT MUTATION; AIDS VIRUS; RETROVIRUS AB Human immunodeficiency virus type 1 (HIV-1) displays both interstrain and intrastrain genetic variability. Virus populations with extensive microheterogeneity have been defined as swarms or quasispecies. Many of the genomes within HIV-1 swarms appear to be defective in one or more genes required for viral replication. It is unclear to what extent defective viruses play a role in the process of HIV-1 infection or in the pathogenesis of AIDS. We have isolated two biologically active HIV-1 clones: LW 12.3, which contains defects in the vif and vpr genes, and MN ST.1, which has a defect in the vpu gene. LW 12.3 is unable to replicate in peripheral blood mononuclear cells (PBMC). The growth of MN-ST.1 in SupT1 cells is marked by a 3-week lag in extracellular virus production and by the presence of unusually abundant viral buds. We demonstrate here that coinfection of PBMC with these two partially defective HIV-1 clones extends the cellular host range of LW 12.3, significantly increases the replication rate of both viral genomes, and eliminates the delay in production observed with the vpu-defective MN ST.I. When the lesions in vpr and vif of LW 12.3 are repaired, the resultant virus grows normally in PBMC. This is also the case when only vif is repaired, indicating that complementation of LW 12.3 in PBMC by MN ST.1 is mediated by vif in trans. The reciprocal complementation results in a dramatic increase of HIV-1 virulence. This two-component model represents a simplified version of the in vivo situation and illustrates one way in which interaction of defective viruses could increase the spread of infection and progression of disease. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. NR 49 TC 39 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1992 VL 66 IS 9 BP 5553 EP 5560 PG 8 WC Virology SC Virology GA JJ198 UT WOS:A1992JJ19800046 PM 1501290 ER PT J AU EARL, PL DOMS, RW MOSS, B AF EARL, PL DOMS, RW MOSS, B TI MULTIMERIC CD4 BINDING EXHIBITED BY HUMAN AND SIMIAN IMMUNODEFICIENCY VIRUS ENVELOPE PROTEIN DIMERS SO JOURNAL OF VIROLOGY LA English DT Note ID SOLUBLE CD4; OLIGOMERIC STRUCTURE; ENDOPLASMIC-RETICULUM; GLYCOPROTEIN; TYPE-1; FUSION; HIV; GP120; INFECTION; REGION AB The envelope (Env) glycoproteins of human and simian immunodeficiency viruses (HIV and SIV) form noncovalently associated oligomers which mediate virus binding to the cell surface and fusion between the viral envelope and plasma membrane. A high-affinity interaction with CD4 is a critical step in this process. In this report, we show that Env protein dimers, but not monomers, can bind two CD4 molecules simultaneously. Multimeric CD4 binding may have important implications for Env protein-CD4 avidity, CD4-induced release of gp120, and subunit-subunit cooperativity during virus membrane fusion as well as for therapeutic strategies. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RP EARL, PL (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. NR 38 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1992 VL 66 IS 9 BP 5610 EP 5614 PG 5 WC Virology SC Virology GA JJ198 UT WOS:A1992JJ19800056 PM 1501294 ER PT J AU MENENDEZARIAS, L RISCO, C DASILVA, PP OROSZLAN, S AF MENENDEZARIAS, L RISCO, C DASILVA, PP OROSZLAN, S TI PURIFICATION OF IMMATURE CORES OF MOUSE MAMMARY-TUMOR VIRUS AND IMMUNOLOCALIZATION OF PROTEIN DOMAINS SO JOURNAL OF VIROLOGY LA English DT Note ID MURINE LEUKEMIA-VIRUS; NUCLEOTIDE-SEQUENCE; MATRIX PROTEIN; GAG GENE; ACID; PARTICLES; MORPHOGENESIS; POLYPROTEINS; RETROVIRUS; EVENTS AB The immature capsids of the mouse mammary tumor virus (MMTV), known as intracytoplasmic A particles, have been isolated from murine L1210 leukemia cells. The diameter of the isolated particles was 80 nm as determined by negative staining. Two polypeptides of 77 and 110 kDa were found to be their major polypeptide components, in agreement with the expected sizes of the Gag and Gag-Pro precursor polypeptides of the mature MMTV proteins. Both polypeptides were recognized by antibodies directed toward the matrix (p10) and capsid (p27) proteins of MMTV. Immunogold labeling of p10 on isolated A particles, visualized by negative staining, showed that this protein is located at the surface of the immature capsids, whereas p27 can be detected only in broken or disrupted particles, suggesting that it has an internal location. These observations were confirmed by immunolabeling of both proteins on thin sections of A particle-producing cells. In addition, the viral protease had a more internal position than p27. Since the sequential order of the viral proteins in the Gag precursor is p10-pp21-p27-p14 and that in Gag-Pro is p10-pp21-p27-p30-protease, our results demonstrate the radial organization of the polypeptide precursors forming the intracytoplasmic A particles. C1 FREDERICK CANC RES & DEV CTR,NCI,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,STRUCT BIOL SECT,FREDERICK,MD 21702. RI Menendez Arias, Luis /G-2436-2016; OI Menendez Arias, Luis/0000-0002-1251-6640 FU NCI NIH HHS [N01-CO-74101] NR 31 TC 14 Z9 15 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1992 VL 66 IS 9 BP 5615 EP 5620 PG 6 WC Virology SC Virology GA JJ198 UT WOS:A1992JJ19800057 PM 1380097 ER PT J AU CHEN, HS KEW, MC HORNBUCKLE, WE TENNANT, BC COTE, PJ GERIN, JL PURCELL, RH MILLER, RH AF CHEN, HS KEW, MC HORNBUCKLE, WE TENNANT, BC COTE, PJ GERIN, JL PURCELL, RH MILLER, RH TI THE PRECORE GENE OF THE WOODCHUCK HEPATITIS-VIRUS GENOME IS NOT ESSENTIAL FOR VIRAL REPLICATION IN THE NATURAL HOST SO JOURNAL OF VIROLOGY LA English DT Note ID PERSISTENT HEPADNAVIRUS INFECTIONS; PRE-C REGION; B VIRUS; E-ANTIGEN; DEFECTIVE VIRUS; REQUISITE ROLE; DNA; ESTABLISHMENT; SECRETION; SEQUENCE AB A number of naturally occurring hepatitis B virus mutants that cannot synthesize the virus precore protein have been identified. Such mutants have been associated with more severe forms of hepatitis, including fulminant hepatitis. The most common mutation observed is a substitution of G to A in the distal precore gene that converts a codon specifying Trp (TGG) to a termination codon (TAG). Using oligonucleotide-directed mutagenesis, we have produced the same point mutation in the precore gene of an infectious clone of woodchuck hepatitis virus (WHV). Transfection of mutant WHV DNA into the livers of adult woodchucks resulted in replication of the mutant in three of three susceptible animals. Levels of virus replication and transient elevations in liver enzymes in serum were similar to those of adult animals infected with wild-type WHV. Virions, found to possess mutant precore genes by polymerase chain reaction amplification and DNA sequencing, were recovered from the serum of one of the animals and inoculated subcutaneously into neonatal woodchucks. They produced infection in all five animals studied. The level of virus replication in neonatal animals infected with this mutant virus was comparable to that found in neonatal woodchucks infected with wild-type WHV, but none of five woodchucks infected with the precore mutant virus as neonates became chronic virus carriers. It was concluded that the precore gene of the WHV genome is not essential for virus replication in the natural host but may be important for chronic infection. C1 NIAID,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT IMMUNOL & INFECT DIS,BALTIMORE,MD 21205. CORNELL UNIV,COLL VET MED,ITHACA,NY 14853. GEORGETOWN UNIV,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20852. FU NIAID NIH HHS [N01-AI-72623, N01-AI-82698] NR 19 TC 101 Z9 103 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1992 VL 66 IS 9 BP 5682 EP 5684 PG 3 WC Virology SC Virology GA JJ198 UT WOS:A1992JJ19800070 PM 1501300 ER PT J AU CHRISCHILLES, EA FOLEY, DJ WALLACE, RB LEMKE, JH SEMLA, TP HANLON, JT GLYNN, RJ OSTFELD, AM GURALNIK, JM AF CHRISCHILLES, EA FOLEY, DJ WALLACE, RB LEMKE, JH SEMLA, TP HANLON, JT GLYNN, RJ OSTFELD, AM GURALNIK, JM TI USE OF MEDICATIONS BY PERSONS 65 AND OVER - DATA FROM THE ESTABLISHED POPULATIONS FOR EPIDEMIOLOGIC STUDIES OF THE ELDERLY SO JOURNALS OF GERONTOLOGY LA English DT Article ID DRUG-USE; PRESCRIPTION; IMPAIRMENT; ADMISSION; HEALTH; AGE AB Data were analyzed from household interviews of four population-based cohorts comprising the Established Populations for Epidemiologic Studies of the Elderly to estimate the prevalence of prescription and nonprescription medication use among community-living elderly and to examine sociodemographic and health factors related to medication use. Prescription drugs were used by 60-68% of men and 68-78% of women. Nonprescription drugs were used by 52-68% of men and 64-76% of women. Use of prescription medications generally increased with age although use of nonprescription drugs was not associated with age. Men and women who smoked or used alcohol in the preceding year frequently took medications. Those who reported more depressive symptoms, impairments in physical functioning, hospitalizations, and had poorer self-perceived health status were most likely to take medications. However, 10-29% of respondents with fair or poor self-perceived health took no prescription medications, and 3-13% took neither prescription nor nonprescription medications. While further research appears warranted into potential overmedication of elders, particularly those with many depressive symptoms, these data suggest that studies of potential underuse among elders with poor health are equally important. C1 HARVARD UNIV,SCH MED,CHANNING LAB,BOSTON,MA 02115. NIA,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. DUKE UNIV,MED CTR,DIV GERIATR MED,DURHAM,NC 27710. UNIV ILLINOIS,COLL PHARM,CHICAGO,IL 60680. DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27710. RP CHRISCHILLES, EA (reprint author), UNIV IOWA,COLL MED,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242, USA. NR 35 TC 150 Z9 152 U1 0 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD SEP PY 1992 VL 47 IS 5 BP M137 EP M144 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA JM624 UT WOS:A1992JM62400012 PM 1512428 ER PT J AU HORIKOSHI, S FUKUDA, K RAY, PE SAWADA, M BRUGGEMAN, LA KLOTMAN, PE AF HORIKOSHI, S FUKUDA, K RAY, PE SAWADA, M BRUGGEMAN, LA KLOTMAN, PE TI A PCR METHOD FOR THE QUANTITATIVE ASSESSMENT OF MESSENGER-RNA FOR LAMININ-A, LAMININ-B1, AND LAMININ-B2 CHAINS SO KIDNEY INTERNATIONAL LA English DT Note ID EXTRACELLULAR-MATRIX COMPONENTS; EXPRESSION; SEQUENCE; PROTEINS; B1-CHAIN; B2-CHAIN; KIDNEY; CELLS; ACID AB Laminin, a basement membrane glycoprotein, is involved in the development of normal kidney and its dysregulation contributes to glomerulosclerosis in renal disease. Studies designed to assess the regulation of this molecule at the level of transcription have been hindered by the relatively low abundance of the mRNA, making standard techniques such as Northern hybridization and RNase protection difficult and inaccurate. In this report, we have utilized the polymerase chain reaction (PCR) to quantitate differences in laminin mRNA expression during normal development of the mouse kidney. We have constructed a synthetic template to be used as an internal standard for mRNA quantitation of laminin chains A, B1 and B2, and beta-actin. This DNA template can be used to generate complementary RNA which can be reverse transcribed and amplified simultaneously with 0.5-mu-g of total cellular mRNA allowing for accurate and absolute quantitation of laminin mRNA by PCR. C1 NIDR,DEV BIOL LAB,BLDG 30,ROOM 433,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 18 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1992 VL 42 IS 3 BP 764 EP 769 DI 10.1038/ki.1992.345 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA JJ445 UT WOS:A1992JJ44500029 PM 1405354 ER PT J AU HOFFMAN, PM CIMINO, EF ROBBINS, DS BROADWELL, RD POWERS, JM RUSCETTI, SK AF HOFFMAN, PM CIMINO, EF ROBBINS, DS BROADWELL, RD POWERS, JM RUSCETTI, SK TI CELLULAR TROPISM AND LOCALIZATION IN THE RODENT NERVOUS-SYSTEM OF A NEUROPATHOGENIC VARIANT OF FRIEND MURINE LEUKEMIA-VIRUS SO LABORATORY INVESTIGATION LA English DT Article DE NEURODEGENERATION; GP70; ENDOTHELIAL CELL; ASTROGLIOSIS ID WILD MOUSE RETROVIRUS; NEUROTROPIC RETROVIRUS; HINDLIMB PARALYSIS; ENVELOPE GENE; DISEASE; INFECTION; MICE; MUTANT; NEUROVIRULENCE; DEGENERATION AB BACKGROUND: We studied PVC-211 murine leukemia virus (MuLV) (1), a neuropathogenic variant of Friend MuLV, to determine its cellular tropism and distribution in the nervous system of infected rats and the factors that affected disease expression. EXPERIMENTAL DESIGN: Rats from five different strains and mice from 3 strains were inoculated intracerebrally or intraperitoneally from birth to 10 days of age and observed for signs of neurologic disease and tumors for 24 weeks. Nervous system pathology, MuLV gp70 expression, and virus production were evaluated weekly for 4 weeks after perinatal infection of Fisher (F344) rats. Blood-brain-barrier integrity and ultrastructure were evaluated in 21-day-old symptomatic infected rats. Microvessel and mixed glial cell cultures were prepared from brains of infected and uninfected 21-day-old F344 rats and evaluated for virus production, MuLV gp70 expression, and the presence of PVC-211 MuLV DNA. RESULTS: Tremor, ataxia, spasticity, and hindlimb weakness occurred in rats and mice as early as 3 weeks after neonatal infection. Severity, latency, and progression varied among mouse and rat strains but exposure to PVC-211 MuLV before 6 days of age was required for disease expression. Rapid PVC-211 MuLV replication in brain capillary endothelial cells (BCEC) early in the perinatal period was followed by widespread astrogliosis, neuropil vacuolation, and finally, neuronal degeneration in the spinal cord, brainstem, cerebellum, and subcortex. MuLV gp70 expression in vivo increased during infection, was restricted to BCEC, but was not associated with perivascular inflammatory infiltrates. BCEC cultured from microvessel preparations but not astrocytes or microglia in mixed glial cell cultures isolated from infected rats contained PVC-211 MuLV DNA, expressed MuLV gp70, and produced infectious virus. CONCLUSIONS: The rapid replication of PVC-211 MuLV that occurs in the nervous system of infected rodents is restricted to BCEC. These infected BCEC appear to play a critical role in initiating the astroglial response in this neurodegenerative process through mechanisms that remain to be defined. C1 UNIV MARYLAND,DEPT NEUROL PATHOL,BALTIMORE,MD 21201. UNIV MARYLAND,DIV NEUROL SURG,BALTIMORE,MD 21201. COLUMBIA PRESBYTERIAN MED CTR,DEPT PATHOL,DIV NEUROPATHOL,NEW YORK,NY 10032. NCI,MOLEC ONCOL LAB,FREDERICK,MD 21701. RP HOFFMAN, PM (reprint author), DEPT VET AFFAIRS MED CTR,RETROVIRUS RES CTR,3900 LOCH RAVEN BLVD,BALTIMORE,MD 21218, USA. FU NIAID NIH HHS [AII-25336] NR 37 TC 50 Z9 50 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD SEP PY 1992 VL 67 IS 3 BP 314 EP 321 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA JP572 UT WOS:A1992JP57200004 PM 1405490 ER PT J AU GOLDSCHMIDTS, WL BHATIA, K JOHNSON, JF AKAR, N GUTIERREZ, MI SHIBATA, D CAROLAN, M LEVINE, A MAGRATH, IT AF GOLDSCHMIDTS, WL BHATIA, K JOHNSON, JF AKAR, N GUTIERREZ, MI SHIBATA, D CAROLAN, M LEVINE, A MAGRATH, IT TI EPSTEIN-BARR-VIRUS GENOTYPES IN AIDS-ASSOCIATED LYMPHOMAS ARE SIMILAR TO THOSE IN ENDEMIC BURKITTS LYMPHOMAS SO LEUKEMIA LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; B-CELLS; MALARIA; PREVALENCE; REGION AB PCR was used to screen EBV-positive lymphomas from endemic and sporadic Burkitt's lymphoma patients, including EBV-positive lymphomas derived from patients with HIV infection. Only 10% of sporadic lymphomas from either North America (1/15) or South America (2/14) were associated with the type 2 EBV strain, whereas 50% (8116) of lymphomas from equatorial Africa and 46% (10/22) of HIV-associated lymphomas were positive for the type 2 strain. These data, in conjuction with previous reports, suggest that the proportions of strain types in Burkitt's lymphoma reflect the proportions of strain types in peripheral lymphocytes, and not simply the prevailing regional strain. The increased association of the type 2 strain in lymphocytes and lymphomas from HIV-infected individuals and from Africa may be a result of intermittent (malaria) or continuous (HIU) compromise of immune function in these populations. C1 NCI,PEDIAT BRANCH,POB,BLDG 10 ROOM 13N240,BETHESDA,MD 20892. UNIV ANKARA,RES CTR,ANKARA,TURKEY. UNIV SO CALIF,LOS ANGELES CTY MED CTR,LOS ANGELES,CA 90033. NR 20 TC 44 Z9 44 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD SEP PY 1992 VL 6 IS 9 BP 875 EP 878 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA JP810 UT WOS:A1992JP81000003 PM 1325581 ER PT J AU WAN, XM FU, TC LONDON, RE AF WAN, XM FU, TC LONDON, RE TI CHARGE DEPENDENCE OF THE DISTRIBUTION OF CONTRAST AGENTS IN RAT CEREBRAL-VENTRICLES SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article ID SIALIC-ACID; BRAIN; SURFACE; CELLS C1 NATL TAIWAN UNIV,COLL MED,DEPT PHYSIOL,TAIPEI 10018,TAIWAN. RP WAN, XM (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 25 TC 6 Z9 6 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD SEP PY 1992 VL 27 IS 1 BP 135 EP 141 DI 10.1002/mrm.1910270113 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JN166 UT WOS:A1992JN16600012 PM 1435199 ER PT J AU LEBIHAN, D TURNER, R AF LEBIHAN, D TURNER, R TI THE CAPILLARY NETWORK - A LINK BETWEEN IVIM AND CLASSICAL PERFUSION SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note ID CEREBRAL BLOOD-FLOW; FREELY DIFFUSIBLE TRACER; COMPUTED-TOMOGRAPHY; BRAIN; NMR; TRANSIT; MOTION; VOLUME; WATER; CATS C1 NHLBI,BETHESDA,MD 20892. RP LEBIHAN, D (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,RM 1C660,BETHESDA,MD 20892, USA. RI Turner, Robert/C-1820-2008 NR 44 TC 129 Z9 130 U1 0 U2 15 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD SEP PY 1992 VL 27 IS 1 BP 171 EP 178 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JN166 UT WOS:A1992JN16600015 PM 1435202 ER PT J AU SONG, LJ STEPHENS, JM KITTUR, S COLLINS, GD NAGEL, JE PEKALA, PH ADLER, WH AF SONG, LJ STEPHENS, JM KITTUR, S COLLINS, GD NAGEL, JE PEKALA, PH ADLER, WH TI EXPRESSION OF C-FOS, C-JUN AND JUN-B IN PERIPHERAL-BLOOD LYMPHOCYTES FROM YOUNG AND ELDERLY ADULTS SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE HUMAN T-CELLS; FOS; JUN; PERIPHERAL BLOOD LYMPHOCYTES; AGING ID MESSENGER-RNA; CELLS; PROTOONCOGENES; RECEPTOR; AP-1; ACTIVATION; GENES; TPA; DNA AB The expression of c-fos, c-jun and jun B proto-oncogenes was studied in phytohemagglutinin (PHA) activated peripheral blood lymphocytes (PBL) from young and aged humans. Specific mRNAs for c-fos and c-jun were detectable within 30 min after cell activation and reached maximal levels within 2 h. Both c-fos and jun B mRNAs decreased to pre-activation levels within 6 h, while c-jun mRNA remained elevated. In PHA-activated PBL, no age-related differences were observed in c-fos or jun B mRNA expression. However, c-jun mRNA levels decreased significantly (1.73 +/- 0.08 vs. 1.16 +/- 0.09 arbitrary units, P < 0.01, young vs. old) in PBL from elderly individuals activated with PHA. Because previous work has demonstrated that T cells from elderly individuals may display normal proliferative responses when activated via the anti-CD2 pathway, c-jun and jun B mRNA expression was also studied in anti-CD2-activated purified T cells. No age-related differences were found in the expression of either of these two proto-oncogenes by anti-CD2 activated T cells. These results suggest that the decreased IL-2 production and proliferative response displayed by PHA-activated PBL from elderly adults may be related to age-related changes in c-jun mRNA expression and in the ratio of c-fos to c-jun mRNA. C1 NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,4940 EASTERN AVE,BALTIMORE,MD 21224. E CAROLINA UNIV,SCH MED,DEPT BIOCHEM,GREENVILLE,NC 27858. FU NIGMS NIH HHS [GM32892] NR 25 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD SEP PY 1992 VL 65 IS 2-3 BP 149 EP 156 DI 10.1016/0047-6374(92)90031-8 PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA JQ911 UT WOS:A1992JQ91100004 PM 1434944 ER PT J AU PUSCHEL, AW WESTERFIELD, M DRESSLER, GR AF PUSCHEL, AW WESTERFIELD, M DRESSLER, GR TI COMPARATIVE-ANALYSIS OF PAX-2 PROTEIN DISTRIBUTIONS DURING NEURULATION IN MICE AND ZEBRAFISH SO MECHANISMS OF DEVELOPMENT LA English DT Article DE BRAIN; ENGRAILED; PAIRED-BOX; SPINAL CORD ID DEVELOPING EXCRETORY SYSTEM; BOX-CONTAINING GENE; PAIRED-BOX; SPINAL-CORD; DROSOPHILA NEUROGENESIS; AXONAL OUTGROWTH; GROWTH CONES; NEURAL-TUBE; EXPRESSION; MURINE AB Members of different vertebrate species share a number of developmental mechanisms and control genes, suggesting that they have similar genetic programs of development. We compared the expression patterns of the Pax-2 protein in Mus musculus and Brachydanio rerio to gain a better understanding of the evolution of developmental control genes. We found that the tissue specificity and the time course of Pax-2 expression relative to specific developmental processes are remarkably similar during the early development of the two organisms. The brain, the optic stalk, the auditory vesicle, the pronephros, and single cells in the spinal cord and the hindbrain express Pax-2 in both species. The Pax-2 expression domain in the prospective brain of E8 mouse embryos has not been described previously. Expression appears first during early neurulation at the junction beween the midbrain and hindbrain. However, there are some differences in Pax-2 expression between the two species. Most notable, expression at the midbrain/hindbrain boundary is no longer detectable after Ell in the mouse. Using monoclonal antibodies, we could exclude that primary neurons express Pax-2 in the zebrafish spinal cord. Our results confirm that Pax genes are highly conserved both in sequences and in expression patterns, indicating that they may have a function during early development that has been conserved during vertebrate evolution. C1 UNIV OREGON,INST NEUROSCI,222 HUESTIS HALL,EUGENE,OR 97403. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. FU NICHD NIH HHS [HD22486] NR 56 TC 141 Z9 141 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD SEP PY 1992 VL 38 IS 3 BP 197 EP 208 DI 10.1016/0925-4773(92)90053-M PG 12 WC Developmental Biology SC Developmental Biology GA JW549 UT WOS:A1992JW54900004 PM 1457381 ER PT J AU VANGALEN, PJM STILES, GL MICHAELS, G JACOBSON, KA AF VANGALEN, PJM STILES, GL MICHAELS, G JACOBSON, KA TI ADENOSINE-A(1) AND ADENOSINE-A(2) RECEPTORS - STRUCTURE-FUNCTION-RELATIONSHIPS SO MEDICINAL RESEARCH REVIEWS LA English DT Review ID ADENYLATE CYCLASE SYSTEM; CYCLIC-AMP PHOSPHODIESTERASE; SEQUENCE-ANALYSIS PROGRAMS; BETA-ADRENERGIC-RECEPTOR; VASCULAR SMOOTH-MUSCLE; HIGH-AFFINITY; A1-ADENOSINE RECEPTORS; GUINEA-PIG; A2-ADENOSINE RECEPTORS; BINDING SUBUNIT C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP VANGALEN, PJM (reprint author), NIDDK,BIOORGAN LAB,BLDG 8A,ROOM B1A-17,BETHESDA,MD 20892, USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 197 TC 125 Z9 125 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD SEP PY 1992 VL 12 IS 5 BP 423 EP 471 DI 10.1002/med.2610120502 PG 49 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JJ385 UT WOS:A1992JJ38500001 PM 1513184 ER PT J AU FOSNAUGH, JS BUNKER, EB PICKWORTH, WB AF FOSNAUGH, JS BUNKER, EB PICKWORTH, WB TI DAILY VARIATION AND EFFECTS OF AMBIENT LIGHT AND CIRCADIAN FACTORS ON THE HUMAN LIGHT REFLEX SO METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY LA English DT Article DE PUPILLOMETRY; LIGHT REFLEX; HUMAN; BINOCULAR SUMMATION ID MORPHINE-INDUCED MYDRIASIS; PUPILLARY; SIZE; CAT AB Measures of pupillary size and the dynamic light reflex are safe and noninvasive methods to quantify and characterize the mechanism and site of drug action. The effects of variations in ambient light and time of day on pupillary measures were determined In dark adapted volunteers (n = 13), ambient light was incrementally increased at <0.1, 4, 40, 100 and 200 foot-candle (ftcd). Subjects adjusted to each light level for 1 min before the light reflex was elicited Replicate measures were collected with the contralateral eye open and covered with an opaque patch. Data were collected every 3 h between 6 a.m. and 9 p.m. The prestimulus diameter of the dark adapted pupil averaged 6.4 mm at <0.1 ftcd and 2.3 mm at 200 ftcd. Constriction amplitude decreased with increases in ambient light from 2.1 mm (<0.1 ftcd) to 0. 2 mm (200 ftcd) while constriction and dilation velocities decreased from 7.7 to 2.8 mm/sec and 4.3 to 2.8 mm/sec, respectively. Time of day effects were small but statistically significant and the interaction of ambient light and time of recording suggests the pupil is differentially sensitive to ambient and phasic light stimuli over the course of the day. A patch over the contralateral eye increased pupil size and velocities of the light reflex. In a second study, 10 volunteers were tested twice a day at 4 and 80 ftcd for four days. While there was wide between subject variability, the within subject differences were small Such baseline data may be useful in describing the normal variations in these increasingly popular indices of drug action. C1 NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224. NR 25 TC 10 Z9 10 U1 1 U2 3 PU J R PROUS SA PI BARCELONA PA APARTADO DE CORREOS 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0379-0355 J9 METHOD FIND EXP CLIN JI Methods Find. Exp. Clin. Pharmacol. PD SEP PY 1992 VL 14 IS 7 BP 545 EP 553 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JZ607 UT WOS:A1992JZ60700009 PM 1287379 ER PT J AU BASSER, PJ AF BASSER, PJ TI INTERSTITIAL PRESSURE, VOLUME, AND FLOW DURING INFUSION INTO BRAIN-TISSUE SO MICROVASCULAR RESEARCH LA English DT Article ID MATHEMATICAL-MODEL; THEORETICAL-MODEL; WATER FLUX; TRANSPORT; DIFFUSION; TORTUOSITY; FRACTION; WALL RP BASSER, PJ (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,MECH ENGN SECT,BETHESDA,MD 20892, USA. RI Kipke, Daryl/A-2167-2009; Basser, Peter/H-5477-2011 NR 30 TC 93 Z9 94 U1 0 U2 10 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD SEP PY 1992 VL 44 IS 2 BP 143 EP 165 DI 10.1016/0026-2862(92)90077-3 PG 23 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT396 UT WOS:A1992JT39600002 PM 1474925 ER PT J AU CAMPO, E PEREZ, M CHARONIS, AA AXIOTIS, CA MERINO, MJ AF CAMPO, E PEREZ, M CHARONIS, AA AXIOTIS, CA MERINO, MJ TI PATTERNS OF BASEMENT-MEMBRANE LAMININ DISTRIBUTION IN NONNEOPLASTIC AND NEOPLASTIC THYROID-TISSUE SO MODERN PATHOLOGY LA English DT Article DE THYROID; LAMININ; BASEMENT MEMBRANE; IMMUNOHISTOCHEMISTRY ID IV COLLAGEN; TUMOR INVASION; CANCER; ANTIGENS; ADENOCARCINOMAS; GLYCOPROTEIN; ENDOTHELIUM; COMPONENTS; CARCINOMAS; METASTASIS AB Laminin, a major basement membrane component, is typically absent or partially lost around the epithelial elements of most invasive carcinomas. To evaluate the distribution of laminin in both primary and metastatic thyroid tumors, we studied 14 benign thyroid lesions (eight adenomas, two Graves' disease, two Hashimoto's thyroiditis, one adenomatous hyperplasia, one nodular goiter), 20 carcinomas (seven papillary, six tall cell variant, four follicular, three Hurthle), and eight metastases (five tall cell variant, three follicular) utilizing a polyclonal antibody against highly purified, nidogen-free laminin. All benign lesions showed positive, linear immunostaining along basement membranes. Partial loss or absence of laminin was seen in the solid areas of all types of thyroid carcinomas examined; well-differentiated papillary and follicular tumors, as well as papillary and follicular areas of more poorly differentiated neoplasms, maintained linear laminin immunostaining in the papillary cores beneath the epithelial cells and around follicles. A similar correlation between laminin deposition and architectural organization was seen in metastatic lesions. Hurthle cell carcinomas had a unique fragmented, pericellular immunostaining pattern around individual tumor cells, suggesting uncontrolled laminin synthesis. Our findings suggest that preservation of laminin production in thyroid tumors reflects their degree of differentiation and that absence of laminin correlates with lack of structural organization rather than reflecting invasive and metastatic potential. C1 NCI,PATHOL LAB,BLDG 10,RM 2N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UNIV MINNESOTA,DEPT PATHOL,MINNEAPOLIS,MN 55455. RI Ain, Kenneth/A-5179-2012; OI Ain, Kenneth/0000-0002-2668-934X; Campo, elias/0000-0001-9850-9793 NR 33 TC 11 Z9 11 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 1992 VL 5 IS 5 BP 540 EP 546 PG 7 WC Pathology SC Pathology GA JP049 UT WOS:A1992JP04900013 PM 1344818 ER PT J AU MACLEOD, CB REPETTI, CF TSOKOS, M AF MACLEOD, CB REPETTI, CF TSOKOS, M TI ENZYMATIC TREATMENTS ON PARAFFIN BLOCKS FOR DNA FLOW-CYTOMETRY SO MODERN PATHOLOGY LA English DT Article DE FLOW CYTOMETRY; PARAFFIN-EMBEDDED TISSUE; ENZYMATIC TREATMENTS; QUALITY OF HISTOGRAMS; TECHNIQUE ID EMBEDDED TISSUE; SECTION THICKNESS; NUCLEI; FRESH; SAMPLES; QUALITY; PLOIDY AB The Hedley method for DNA ploidy analysis on paraffin-embedded tissue allows retrospective studies of large numbers of common and rare tumors for which treatment, progression, and outcome are known. However, the technique is cumbersome and has many variables, only some of which can be controlled at the time of laboratory analysis. We performed DNA ploidy analyses on two blocks from two islet cell tumors and on five blocks from two colon carcinomas. Sections of 50-mu-m thickness were deparaffinized in xylene, rehydrated in graded alcohols and in distilled water, and disaggregated with various enzymatic treatments: 0.05% pepsin (30 and 90 min), 0.5% pepsin (30 and 90 min), 0.05% protease (60 min), and 0.1% protease (60 min). The cell suspensions obtained were filtered, washed in PBS, and visually evaluated in a hemocytometer. Nuclei were treated with RNAse (0.1%) and stained with 50-mu-g/ml propidium iodide. Results were evaluated with the following criteria: (a) recovery of DNA aneuploid and/or G2M cells (cell-cycle analysis and visual evaluation); (b) coefficient of variation of the major peak (DNA diploid or DNA aneuploid depending on the case); (c) amount of debris (background events and visual evaluation); (d) mean channel for the G0G1 peak; (e) event rate; and (f) G2M/G0G1 ratio. The best results were observed with 0.05% protease when there was tissue necrosis and hence cell fragility, with 0.1% protease when there was significant tissue fibrosis, and with 0.05% pepsin (90 min) when there were intact cellular specimens without fibrous entrapment. The original procedure using 0.5% pepsin for 30 min produced less cell recovery, and histogram quality similar to or worse than these modifications in all cases studied. This preliminary study suggests that the histogram quality can be improved by modification of the enzymatic treatment, based partly on light microscopic evaluation of the tumors prior to such treatment. C1 NCI,DEPT PATHOL,ULTRASTRUCT PATHOL SECT,BETHESDA,MD 20892. AMER MED LABS INC,DEPT IMMUNOPATHOL & FLOW CYTOMETRY,FAIRFAX,VA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 1992 VL 5 IS 5 BP 569 EP 574 PG 6 WC Pathology SC Pathology GA JP049 UT WOS:A1992JP04900020 PM 1344822 ER PT J AU CAPPAI, R KASLOW, DC PETERSON, MG COWMAN, AF ANDERS, RF KEMP, DJ AF CAPPAI, R KASLOW, DC PETERSON, MG COWMAN, AF ANDERS, RF KEMP, DJ TI CLONING AND ANALYSIS OF THE RESA-2 GENE - A DNA HOMOLOG OF THE RING-INFECTED ERYTHROCYTE SURFACE-ANTIGEN GENE OF PLASMODIUM-FALCIPARUM SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE PLASMODIUM-FALCIPARUM; CLONING; PSEUDOGENE ID HUMAN MALARIA PARASITE; INHIBIT MEROZOITE INVASION; AMINO-ACID SEQUENCE; TUBULIN GENES; ALPHA-TUBULIN; HUMAN-ANTIBODIES; EXPRESSION; AMPLIFICATION; PROTEINS; ISOLATE AB We have cloned and sequenced a homologue of the ring-infected erythrocyte surface antigen (RESA) gene from Plasmodium falciparum designated RESA-2. Two reading frames with high homology to exon 1 and exon 2 of RESA at both the nucleotide and amino acid levels were identified in the RESA-2 sequence. However, RESA-2 does not contain either of the blocks of tandem repeats present in RESA. The lack of an RNA transcript in either asexual or sexual stage parasites and the presence of an in-frame stop codon in the second reading frame suggests RESA-2 could be a pseudogene. Its lack of expression in asexual stages demonstrates that it does not complement the RESA deletion in isolate FCR3. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP CAPPAI, R (reprint author), ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,PARKVILLE,VIC 3050,AUSTRALIA. RI Cappai, Roberto/B-3347-2010; Cowman, Alan/C-7642-2013 OI Cappai, Roberto/0000-0002-9505-8496; Cowman, Alan/0000-0001-5145-9004 NR 32 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD SEP PY 1992 VL 54 IS 2 BP 213 EP 222 DI 10.1016/0166-6851(92)90113-X PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA JM631 UT WOS:A1992JM63100008 PM 1435860 ER PT J AU ZHEN, WP LINK, CJ OCONNOR, PM REED, E PARKER, R HOWELL, SB BOHR, VA AF ZHEN, WP LINK, CJ OCONNOR, PM REED, E PARKER, R HOWELL, SB BOHR, VA TI INCREASED GENE-SPECIFIC REPAIR OF CISPLATIN INTERSTRAND CROSS-LINKS IN CISPLATIN-RESISTANT HUMAN OVARIAN-CANCER CELL-LINES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-REPAIR; GLUTATHIONE DEPLETION; ACQUIRED-RESISTANCE; CYTO-TOXICITY; CHO CELLS; CIS-DIAMMINEDICHLOROPLATINUM(II); PLATINUM; ADDUCTS; MECHANISM; REMOVAL AB We have studied several aspects of DNA damage formation and repair in human ovarian cancer cell lines which have become resistant to cisplatin through continued exposure to the anticancer drug. The resistant cell lines A2780/cp70 and 2008/c13*5.25 were compared with their respective parental cell lines, A2780 and 2008. Cells in culture were treated with cisplatin, and the two main DNA lesions formed, intrastrand adducts and interstrand cross-links, were quantitated before and after repair incubation. This quantitation was done for total genomic lesions and at the level of individual genes. In the overall genome, the initial frequency of both cisplatin lesions assayed was higher in the parental than in the derivative resistant cell lines. Nonetheless, the total genomic repair of each of these lesions was not increased in the resistant cells. These differences in initial lesion frequency between parental and resistant cell lines were not observed at the gene level. Resistant and parental cells had similar initial frequencies of intrastrand adducts and interstrand cross-links in the dihydrofolate reductase (DHFR) gene and in several other genes after cisplatin treatment of the cells. There was no increase in the repair efficiency of intrastrand adducts in the DHFR gene in resistant cell lines compared with the parental partners. However, a marked and consistent repair difference between parental and resistant cells was observed for the gene-specific repair of cisplatin interstrand cross-links. DNA interstrand cross-links were removed from three genes, the DHFR, multidrug resistance (MDR1), and delta-globin genes, much more efficiently in the resistant cell lines than in the parental cell lines. Our findings suggest that acquired cellular resistance to cisplatin may be associated with increased gene-specific DNA repair efficiency of a specific lesion, the interstrand cross-link. C1 NCI,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C-25,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. NR 35 TC 201 Z9 205 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1992 VL 12 IS 9 BP 3689 EP 3698 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JK343 UT WOS:A1992JK34300003 PM 1380646 ER PT J AU STEPHENS, RM SITHANANDAM, G COPELAND, TD KAPLAN, DR RAPP, UR MORRISON, DK AF STEPHENS, RM SITHANANDAM, G COPELAND, TD KAPLAN, DR RAPP, UR MORRISON, DK TI 95-KILODALTON B-RAF SERINE THREONINE KINASE - IDENTIFICATION OF THE PROTEIN AND ITS MAJOR AUTOPHOSPHORYLATION SITE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; COMPLETE CODING SEQUENCE; PC12 PHEOCHROMOCYTOMA CELLS; TRK PROTOONCOGENE PRODUCT; TYROSINE PHOSPHORYLATION; MOLECULAR-CLONING; BINDING DOMAINS; EGF-RECEPTOR; NGF RECEPTOR; LOW-AFFINITY AB B-Raf, a member of the Raf family of serine/threonine kinases, is expressed primarily in the brain and in the nervous system. In this study, the biochemical properties of the B-Raf protein were investigated in nerve growth factor (NGF)-responsive cell lines and in brain tissues. B-Raf was identified by using phosphopeptide mapping analysis and cDNA analysis as a 95-kDa protein which is primarily localized in the cytosol. NGF rapidly stimulated both serine and threonine phosphorylation in vivo and autophosphorylation activity in vitro of the B-Raf protein. In PC12 cells, B-Raf autokinase activity was induced by both differentiation factors and mitogens, with maximal activity observed after 5 min of factor addition. B-Raf kinase activity was also observed following NGF treatment of SH-SY5Y neuroblastoma cells and in adult mouse brain and hippocampus. Induction of B-Raf kinase activity in NGF-treated PC12 cells required expression of kinase-active trk receptors. Exogenous substrates or a peptide containing the autophosphorylation site became phosphorylated when added to immune complex kinase assays and reduced the in vitro autophosphorylation activity of B-Raf, suggesting that in vitro autophosphorylation sites and exogenous substrates compete for active sites of the B-Raf kinase. Finally, the major in vitro autophosphorylation site of B-Raf was identified as threonine 372 in the conserved region 2 domain. A threonine residue is present at similar positions in all three mammalian Raf family members and may represent a regulatory site for these proteins. C1 NCI, FREDERICK CANC RES & DEV CTR, MOLEC MECH CARCINOGENESIS LAB, POB B, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, PROT STRUCT GRP, FREDERICK, MD 21702 USA. NCI, VIRAL CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. PROGRAM RESOURCES INC DYNCORP, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 64 TC 69 Z9 73 U1 5 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1992 VL 12 IS 9 BP 3733 EP 3742 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JK343 UT WOS:A1992JK34300008 PM 1508179 ER PT J AU CUTLER, ML BASSIN, RH ZANONI, L TALBOT, N AF CUTLER, ML BASSIN, RH ZANONI, L TALBOT, N TI ISOLATION OF RSP-1, A NOVEL CDNA CAPABLE OF SUPPRESSING V-RAS TRANSFORMATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; ADENYLYL CYCLASE GENE; SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; PRODUCT; YEAST; CELLS; GAP; IDENTIFICATION; ONCOGENES AB Using an expression cloning assay, we have isolated a novel cDNA, referred to as rsp-1, which suppresses the v-Ras-transformed phenotype. When introduced into NIH 3T3 fibroblasts under the control of a metallothionein promoter, rsp-1 confers resistance to v-Ras, but not to v-Mos or v-Src, and inhibits growth of the cells. The rsp-1 cDNA contains a 831-bp open reading frame encoding a 277-amino-acid leucine-rich protein. The rsp-1 cDNA exhibits no significant homology to sequences in the DNA data bases. However, searches of the protein data bases revealed that it contains a series of leucine-based repeats which are homologous to the leucine repeats found in the regulatory region of the yeast adenylyl cyclase. rsp-1 specific RNA is detectable in a wide variety of cell lines and tissues, and the gene is conserved among eukaryotic species. These data suggest that rsp-1 plays a role in Ras signal transduction. RP CUTLER, ML (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892, USA. NR 36 TC 70 Z9 72 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1992 VL 12 IS 9 BP 3750 EP 3756 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JK343 UT WOS:A1992JK34300010 PM 1508180 ER PT J AU MOLLOY, CJ FLEMING, TP BOTTARO, DP CUADRADO, A AARONSON, SA AF MOLLOY, CJ FLEMING, TP BOTTARO, DP CUADRADO, A AARONSON, SA TI PLATELET-DERIVED GROWTH-FACTOR STIMULATION OF GTPASE-ACTIVATING PROTEIN TYROSINE PHOSPHORYLATION IN CONTROL AND C-H-RAS-EXPRESSING NIH 3T3 CELLS CORRELATES WITH P21(RAS) ACTIVATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SIGNAL TRANSDUCTION; EGF-RECEPTOR; SACCHAROMYCES-CEREVISIAE; KINASE-ACTIVITY; PDGF RECEPTOR; GAP; GAMMA; TRANSFORMATION; INDUCTION; OVEREXPRESSION AB Platelet-derived growth factor (PDGF) stimulation of NIH 3T3 cells leads to the rapid tyrosine phosphorylation of the GTPase-activating protein (GAP) and an associated 64- to 62-kDa tyrosine-phosphorylated protein (p64/62). To assess the functions of these proteins, we evaluated their phosphorylation state in normal NIH 3T3 cells as well as in cells transformed by oncogenically activated v-H-ras or overexpression of c-H-ras genes. No significant GAP tyrosine phosphorylation was observed in unstimulated cultures, while PDGF-BB induced rapid tyrosine phosphorylation of GAP in all cell lines analyzed. In NIH 3T3 cells, we found that PDGF stimulation led to the recovery of between 37 and 52% of GAP molecules by immunoprecipitation with monoclonal antiphosphotyrosine antibodies. Furthermore, PDGF exposure led to a rapid and sustained increase in the levels of p21ras bound to GTP, with kinetics similar to those observed for GAP tyrosine phosphorylation. The PDGF-induced increases in GTP-bound p21ras in NIH 3T3 cells were comparable to the steady-state level observed in serum-starved c-H-ras-overexpressing transformants, conditions in which these cells maintained high rates of DNA synthesis. These results imply that the level of p21ras activation following PDGF stimulation of NIH 3T3 cells is sufficient to support mitogenic stimulation. Addition of PDGF to c-H-ras-overexpressing cells also resulted in a rapid and sustained increase in GTP-bound p21ras. In these cells GAP, but not p64/62, showed increased tyrosine phosphorylation, with kinetics similar to those observed for increased GTP-bound p21ras. All of these findings support a role for GAP tyrosine phosphorylation in p21ras activation and mitogenic signaling. C1 NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,ROOM 1E24,BETHESDA,MD 20892. RI Bottaro, Donald/F-8550-2010; Molloy, Christopher/A-6821-2013; OI Bottaro, Donald/0000-0002-5057-5334; Molloy, Christopher/0000-0003-2964-6166; Cuadrado, Antonio/0000-0002-3444-9012 NR 44 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1992 VL 12 IS 9 BP 3903 EP 3909 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JK343 UT WOS:A1992JK34300026 PM 1508192 ER PT J AU MORSE, RH ROTH, SY SIMPSON, RT AF MORSE, RH ROTH, SY SIMPSON, RT TI A TRANSCRIPTIONALLY ACTIVE TRANSFER-RNA GENE INTERFERES WITH NUCLEOSOME POSITIONING INVIVO SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEASE-SENSITIVE REGIONS; PROTEIN-DNA INTERACTIONS; TUMOR VIRUS PROMOTER; SOMATIC-CELL NUCLEI; SACCHAROMYCES-CEREVISIAE; POLYMERASE-III; NUCLEOTIDE-SEQUENCE; CHROMATIN STRUCTURE; 5'-FLANKING REGION; PLASMID CHROMATIN AB Incorporation into a positioned nucleosome of a cis-acting element essential for replication in Saccharomyces cerevisiae disrupts the function of the element in vivo [R. T. Simpson, Nature (London) 343:387-389, 1990]. Furthermore, nucleosome positioning has been implicated in repression of transcription by RNA polymerase II in yeast cells. We have now asked whether the function of cis-acting elements essential for transcription of a gene transcribed by RNA polymerase III can be similarly affected. A tRNA gene was fused to either of two nucleosome positioning signals such that the predicted nucleosome would incorporate near its center the tRNA start site and essential A-box element. These constructs were then introduced into yeast cells on stably maintained, multicopy plasmids. Competent tRNA genes were transcribed in vivo and were not incorporated into positioned nucleosomes. Mutated, inactive tRNA genes were incorporated into nucleosomes whose positions were as predicted. This finding demonstrates that the transcriptional competence of the tRNA gene determined its ability to override a nucleosome positioning signal in vivo and establishes that a hierarchy exists between cis-acting elements and nucleosome positioning signals. RP MORSE, RH (reprint author), NIDDKD,CELLULAR & DEV BIOL LAB,BLDG 6,ROOM B1-26,BETHESDA,MD 20892, USA. OI Morse, Randall/0000-0003-0000-8718 NR 76 TC 73 Z9 73 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1992 VL 12 IS 9 BP 4015 EP 4025 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JK343 UT WOS:A1992JK34300038 PM 1508199 ER PT J AU TAN, TH HUANG, GP SICA, A GHOSH, P YOUNG, HA LONGO, DL RICE, NR AF TAN, TH HUANG, GP SICA, A GHOSH, P YOUNG, HA LONGO, DL RICE, NR TI KAPPA-B SITE-DEPENDENT ACTIVATION OF THE INTERLEUKIN-2 RECEPTOR ALPHA-CHAIN GENE PROMOTER BY HUMAN C-REL SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSFORMED LYMPHOID-CELLS; DNA-BINDING SUBUNIT; AVIAN RETICULOENDOTHELIOSIS VIRUS; NECROSIS-FACTOR-ALPHA; V-REL; TRANSCRIPTION FACTORS; CELLULAR PROTEINS; ONCOGENE PRODUCT; PROTO-ONCOGENE; PROTOONCOGENE PRODUCT AB The cis-acting control elements of the interleukin-2 receptor alpha-chain (IL-2R-alpha) gene contain a potent kappa-B-like enhancer whose activity can be induced by various mitogenic stimuli. Recent cloning of the p50 and p65 subunits of the kappa-B-binding protein NF-kappa-B complex revealed a striking sequence homology of these proteins with the c-rel proto-oncogene product (c-Rel). On the basis of this homology, we examined the potential role of c-Rel in controlling IL-2R-alpha transcription. We now demonstrate that the recombinant human c-Rel protein binds to the kappa-B element in the IL-2R-alpha promoter and results in alteration of the DNA structure in the adjacent downstream regulatory elements containing the CArG box and the GC box. We found that human c-Rel can activate transcription from the IL-2R-alpha promoter, but not the kappa-B-containing human immunodeficiency virus type 1 promoter, upon cotransfection into Jurkat T cells. Furthermore, truncation of the carboxyl terminus of c-Rel results in a c-Rel mutant (Rel(NA)) that (i) localizes exclusively in the nucleus and (ii) acts in synergy with wild-type c-Rel in activating transcription from the KB site of the IL-2R-alpha promoter. Finally, induction of surface IL-2R-alpha expression coincides with the induced levels of endogenous c-Rel and induced c-Rel binding to the IL-2R-alpha-kappa-B site. Our study identified c-Rel as one component of the Rel/NF-kappa-B-family proteins involved in the kappa-B-dependent activation of IL-2R-alpha gene expression. Furthermore, our results suggest that a Rel(NA)-like cellular factor (e.g., NF-kappa-B p50 or p49 subunit) acts in synergy with c-Rel during T-cell activation. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC VIROL & CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RI Tan, Tse-Hua/E-3983-2010 OI Tan, Tse-Hua/0000-0003-4969-3170 FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 71 TC 91 Z9 91 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1992 VL 12 IS 9 BP 4067 EP 4075 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JK343 UT WOS:A1992JK34300043 PM 1508203 ER PT J AU HULTSCH, T MARTIN, R HOHMAN, RJ AF HULTSCH, T MARTIN, R HOHMAN, RJ TI THE EFFECT OF THE IMMUNOPHILIN LIGANDS RAPAMYCIN AND FK506 ON PROLIFERATION OF MAST-CELLS AND OTHER HEMATOPOIETIC-CELL LINES SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CYTOSOLIC BINDING-PROTEIN; PEPTIDYL-PROLYL ISOMERASE; CYCLOSPORINE-A; T-CELL; IMMUNOSUPPRESSANT FK506; SIGNAL TRANSDUCTION; GROWTH-FACTOR; RECEPTOR; INTERLEUKIN-3; CYCLOPHILIN AB The immunosuppressive drugs FK506 and cyclosporin A have an identical spectrum of activities with respect to IgE receptor (FcepsilonRI)-mediated exocytosis from mast cells and T cell receptor-mediated transcription of IL-2. These findings suggest a common step in receptor-mediated signal transduction leading to exocytosis and transcription and imply that immunosuppressive drugs target specific signal transduction pathways, rather than specific cell types. This hypothesis is supported by studies on the effect of rapamycin on IL-3 dependent proliferation of the rodent mast cell line PT18. Rapamycin inhibits proliferation of PT18 cells, achieving a plateau of 80% inhibition at 1 nM. This inhibition is prevented in a competitive manner by FK506, a structural analogue of rapamycin. Proliferation of rat basophilic leukemia cells and WEHI-3 cells was also inhibited, at doses comparable to those shown previously to inhibit IL-2-dependent proliferation of cytotoxic T lymphocyte line (CTLL) cells. In contrast, proliferation of A-431 cells, a epidermoid cell line, was not affected by rapamycin. DNA histograms indicate that complexes formed between the rapamycin-FK506-binding protein (FKBP) and rapamycin arrest-proliferating PT18 cells in the G0/G1-phase. It is concluded that FKBP-rapamycin complexes may inhibit proliferative signals emanating from IL-3 receptors, resulting in growth arrest of cytokine-dependent, hematopoietic cells. RP HULTSCH, T (reprint author), NIAID,ALLERG DIS SECT,CLIN INVEST LAB,BETHESDA,MD 20892, USA. NR 38 TC 32 Z9 34 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 IS 9 BP 981 EP 987 PG 7 WC Cell Biology SC Cell Biology GA JR057 UT WOS:A1992JR05700005 PM 1384815 ER PT J AU ALBINI, A POGGI, L MELCHIORI, A PELLEGRINI, R DEFILIPPI, P GENTLEMAN, S CHADER, GJ NOONAN, DM AF ALBINI, A POGGI, L MELCHIORI, A PELLEGRINI, R DEFILIPPI, P GENTLEMAN, S CHADER, GJ NOONAN, DM TI LAMININ IS AN ANTIADHESIVE PROTEIN WHICH PROMOTES RETINOBLASTOMA CELL-DIFFERENTIATION - INVESTIGATION OF THE CELL-SURFACE MOLECULES INVOLVED IN LAMININ-RETINOBLASTOMA CELL-INTERACTIONS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 IST,I-16132 GENOA,ITALY. INT,I-20133 MILAN,ITALY. UNIV TURIN,I-10126 TURIN,ITALY. NEI,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A72 EP A72 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500419 ER PT J AU AMBESIIMPIOMBATO, FS CURCIO, F DEGRASSI, A PERRELLA, G COON, HG AF AMBESIIMPIOMBATO, FS CURCIO, F DEGRASSI, A PERRELLA, G COON, HG TI LONG-TERM GROWTH AND PRELIMINARY CHARACTERIZATION OF DIFFERENTIATED THYROID-CELL STRAINS FROM NORMAL HUMAN DONORS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract ID RAT C1 UNIV UDINE,IST PATOL CLIN & SPERIMENTALE,I-33100 UDINE,ITALY. NCI,BETHESDA,MD 20892. RI Curcio, Francesco/K-4669-2014 NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A275 EP A275 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25501599 ER PT J AU ARCHER, TK LEFEBVRE, P WOLFORD, RG ZANIEWSKI, E HAGER, GL AF ARCHER, TK LEFEBVRE, P WOLFORD, RG ZANIEWSKI, E HAGER, GL TI TRANSCRIPTION FACTOR BINDING AT THE MMTV PROMOTER INVIVO SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV WESTERN ONTARIO,DEPT OB GYN & BIOCHEM,LONDON N6A 3K7,ONTARIO,CANADA. NCI,HORMONE ACT & ONCOGENESIS SECT,LMV,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A96 EP A96 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500556 ER PT J AU BEHRENS, TW YEWDELL, JW STAUDT, LS AF BEHRENS, TW YEWDELL, JW STAUDT, LS TI CLONING OF A LYMPHOID SPECIFIC TYPE-II INTEGRAL MEMBRANE-PROTEIN LOCALIZED TO THE ENDOPLASMIC-RETICULUM SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NIAID,LVD,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A33 EP A33 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500187 ER PT J AU BROCK, MA COLLINS, GD ADLER, WH CHREST, FJ AF BROCK, MA COLLINS, GD ADLER, WH CHREST, FJ TI ISOLATION OF RESTING CD4+ AND CD8+ POPULATIONS OF MURINE LYMPHOCYTES USING MAGNETIC BEADS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A91 EP A91 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500531 ER PT J AU BRZESKA, H KULESZALIPKA, D BAINES, I KORN, ED AF BRZESKA, H KULESZALIPKA, D BAINES, I KORN, ED TI CA-2+-CALMODULIN INHIBITION OF THE PHOSPHORYLATION OF ACANTHAMOEBA MYOSIN-IA BY MYOSIN-I HEAVY-CHAIN KINASE (MIHC KINASE) SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A42 EP A42 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500240 ER PT J AU BUBB, MR BAINES, IC KORN, ED AF BUBB, MR BAINES, IC KORN, ED TI PROFILIN ISOFORM DISTRIBUTION IN ACANTHAMOEBA-CASTELLANII SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A42 EP A42 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500238 ER PT J AU CASTRONOVO, V BALDET, M MASSA, SM SOBEL, ME COOPER, DN AF CASTRONOVO, V BALDET, M MASSA, SM SOBEL, ME COOPER, DN TI RECOMBINANT SOLUBLE LECTIN L-14 MODULATES INTERACTIONS BETWEEN HUMAN A2058 MELANOMA-CELLS AND LAMININ SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,TUMOR INVAS & METASTASIS SECT,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,LANGLEY PORTER NEUROPSYCHIAT INST,SAN FRANCISCO,CA 94143. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A73 EP A73 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500423 ER PT J AU COOL, DR FENGER, M HWANG, VK LOH, YP AF COOL, DR FENGER, M HWANG, VK LOH, YP TI EXPRESSION AND INTRACELLULAR TARGETING OF PROOPIOMELANOCORTIN IN THE NEUROBLASTOMA CELL-LINE, NEURO-2A SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,LDN,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A56 EP A56 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500322 ER PT J AU COXEY, RA PENTCHEV, PG CAMPBELL, G BLANCHETTEMACKIE, EJ AF COXEY, RA PENTCHEV, PG CAMPBELL, G BLANCHETTEMACKIE, EJ TI DIFFERENTIAL ACCUMULATION OF CHOLESTEROL IN GOLGI COMPARTMENTS OF NORMAL AND NIEMANN-PICK TYPE-C FIBROBLASTS INCUBATED WITH LDL - A CYTOCHEMICAL FREEZE-FRACTURE STUDY SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIADDKD,LCDB,BETHESDA,MD 20892. NINCDS,DMNB,BETHESDA,MD 20892. NIH,DCRT,LSM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A118 EP A118 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500681 ER PT J AU DASSO, M AF DASSO, M TI THE ASSOCIATION OF RCC1, A REGULATOR OF CHROMOSOME CONDENSATION, WITH PURIFIED CHROMATIN TEMPLATES AND WITH CHROMATIN IN XENOPUS EGG EXTRACTS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A133 EP A133 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500773 ER PT J AU DOHERTY, MM NETTESHEIM, P FERRIOLA, PC AF DOHERTY, MM NETTESHEIM, P FERRIOLA, PC TI REGULATION OF EPIDERMAL GROWTH-FACTOR RECEPTOR IN RAT TRACHEAL EPITHELIAL (RTE) CELLS AS A FUNCTION OF PROLIFERATIVE STATE SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27514. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A28 EP A28 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500158 ER PT J AU FERREIRA, A KINCAID, RL KOSIK, KS AF FERREIRA, A KINCAID, RL KOSIK, KS TI CALCINEURIN LOCALIZATION AT THE GROWING TIPS OF NEURITES DEPENDS UPON INTACT CYTOSKELETAL COMPONENTS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. NIAAA,BETHESDA,MD 20852. NR 1 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A359 EP A359 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25502084 ER PT J AU FERRIOLA, PC CARTER, CA RUSNAK, DW NETTESHEIM, P AF FERRIOLA, PC CARTER, CA RUSNAK, DW NETTESHEIM, P TI REGULATION OF CYTOSKELETAL AND EXTRACELLULAR-MATRIX COMPONENTS BY THE TGF-ALPHA/EGF RECEPTOR PATHWAY IN RAT TRACHEAL EPITHELIAL (RTE) CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A233 EP A233 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25501352 ER PT J AU FRIEDMAN, TC CHEN, HC LOH, YP AF FRIEDMAN, TC CHEN, HC LOH, YP TI A UNIQUE SERINE CARBOXYL-TERMINAL ADRENOCORTICOTROPIN-CLEAVING ENZYME IN BOVINE INTERMEDIATE LOBE SECRETORY VESICLE MEMBRANES SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,LDN,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A193 EP A193 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25501122 ER PT J AU FUKUI, Y JUNG, G HAMMER, JA AF FUKUI, Y JUNG, G HAMMER, JA TI LOCALIZATION OF DICTYOSTELIUM MYOSIN IB AND ID WITH ISOFORM-SPECIFIC ANTIBODIES SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,SCH MED,CMSB,CHICAGO,IL 60611. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A44 EP A44 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500254 ER PT J AU GANGULY, C MARTIN, B BUBB, MR KORN, ED AF GANGULY, C MARTIN, B BUBB, MR KORN, ED TI A STRUCTURAL DIFFERENCE BETWEEN DEPHOSPHORYLATED AND PHOSPHORYLATED MYOSIN-II FROM A-CASTELLANII SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NIMH,CLIN NEUROBIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A42 EP A42 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500243 ER PT J AU GAO, B EISENBERG, E GREENE, D AF GAO, B EISENBERG, E GREENE, D TI BINDING OF NUCLEOTIDE TO THE BOVINE BRAIN UNCOATING ATPASE SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A58 EP A58 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500337 ER PT J AU GAO, J TIFFANY, HL AHUJA, SK MCDERMOTT, D DURSTIN, MA MURPHY, PM AF GAO, J TIFFANY, HL AHUJA, SK MCDERMOTT, D DURSTIN, MA MURPHY, PM TI THE N-FORMYL PEPTIDE RECEPTOR FAMILY IN MOUSE AND MAN SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A87 EP A87 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500507 ER PT J AU GOSIEWSKA, A WILSON, S PETERKOFSKY, B AF GOSIEWSKA, A WILSON, S PETERKOFSKY, B TI ROLE OF INSULIN-LIKE GROWTH-FACTOR (IGF)-BINDING PROTEINS IN THE REGULATION OF COLLAGEN EXPRESSION IN VITAMIN-C-DEFICIENT OR FASTED GUINEA-PIGS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A142 EP A142 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500820 ER PT J AU GUO, N VOGEL, T NEGRE, E ZABRENETZKY, VS KRUTZSCH, HC ROBERTS, DD AF GUO, N VOGEL, T NEGRE, E ZABRENETZKY, VS KRUTZSCH, HC ROBERTS, DD TI INTERACTIONS OF THE BREAST-CARCINOMA CELL-LINE MDA-MB-435S WITH THROMBOSPONDIN ARE MEDIATED BY SULFATED PROTEOGLYCANS AND BETA-INTEGRINS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1992 VL 3 SU S BP A72 EP A72 PG 1 WC Cell Biology SC Cell Biology GA JR255 UT WOS:A1992JR25500414 ER EF